Proteopedia - User contributions [en]

https://proteopedia.org/api.php?action=feedcontributions&feedformat=atom&user=Bashir+Noor Proteopedia - User contributions [en] 2026-09-22T00:05:46Z User contributions MediaWiki 1.43.8 https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2588683 XPD Helicase (3CRV) 2016-04-27T21:03:38Z

<p>Bashir Noor: </p> <hr /> <div><StructureSection load='3CRV' size='450' side='right' scene='72/728075/Reset/2' caption='XPD helicase, 3CRV'><br /> <br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) helicase is a subunit of [http://proteopedia.org/wiki/index.php/Category:Tfiih Transcription Factor IIH (TFIIH)], which aids in [http://proteopedia.org/wiki/index.php/Category:Transcription_initiation transcription initiation] and DNA repair. XPD helicse unwinds DNA, allowing other [http://proteopedia.org/wiki/index.php/Category:Dna-repair DNA repair enzymes] to access and correct damaged regions in the DNA. XPD helicase helps to fix DNA damaged by ultraviolet (UV) light radiation, therefore mutations in XPD helicase results in diseases characterized by light sensitivity. <br /> <br /> == Structure ==<br /> XPD helicase's catalytic core (<scene name='72/728075/Domains/3'>Figure 1</scene>) is composed of four domains, HD1 (green), HD2 (red), 4FeS (brown), and Arch (blue) domains, and six motifs<ref name="Lifuss">PMID: 18510924 </ref>. The HD1 and HD2 domains form the ATP-Binding Interface.The 4FeS domain contains Cysteines 88, 102, 105, and 137 in which the Sulfur-Iron binding occurs (pink), the complex has the role of detecting DNA damage<ref name="Lifuss">PMID: 18510924 </ref>. ssDNA binding is facilitated by the 4FeS domain's Fe-S region and a channel is formed with HD1 and Arch Domains to form a passage way for the ssDNA <ref name="Lifuss">PMID: 18510924 </ref>. Positively charged residues along the channel are paired with negatively charged residues to allow subsequent ssDNA binding and movement along the ssDNA. HD2 domain and the Arch domain form the HD2 gateway which is associated with sensing bulky DNA damage as well<ref name="Lifuss">PMID: 18510924 </ref>. The motif's (<scene name='72/728075/Motifs/3'>Figure 2</scene>), I (31-60, red), II (177-186, blue), III (317-327, green), IV (394-408, brown), V (439-455, purple) and VI (501-517, orange), all play a role in both ATP and DNA binding<ref name="Lifuss">PMID: 18510924 </ref>. Motif's I, II, V, and VI all form the ATP binding site at the HD1 and HD2 interface (<scene name='72/728075/Atp_binding/2'>Figure 3</scene>)<ref name="Lifuss">PMID: 18510924 </ref>. Motif's IV, V, and VI within the HD2 domain form the gateway channel for DNA binding (<scene name='72/728075/Hd2_gate/2'>Figure 4</scene>)<ref name="Lifuss">PMID: 18510924 </ref>.<br /> (<scene name='72/728075/Reset/2'>Reset Protein</scene>)<br /> <br /> == Function ==<br /> XPD helicase is an essential subunit of the general transcription factor IIH (TFIIH), which is a complex that, along with other general transcription factors, helps to initiate transcription and repair damaged DNA <ref name="Mydikova">PMID: 20429618</ref>. XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme <ref name="Lifuss">PMID: 18510924 </ref>. Helicases are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes, like polymerases, can act upon the DNA <ref name="Tuteja">PMID: 15128295 </ref>. In the context of DNA repair, helicases unwind DNA and other enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to UV radiation, adjacent nucleotide bases, often thymines, can react and form bulky pyrimidine dimers, which can block enzymes that work on DNA <ref name="Vink">PMID: 11809365 </ref>. For example, during DNA replication, [http://proteopedia.org/wiki/index.php/Category:Thymine_Dimers thymine dimers] do not fit into the active site of DNA polymerases smoothly, sometimes resulting in mismatched nucleotides. To fix this type of damage on single strands of DNA, cells employ a process called [http://proteopedia.org/wiki/index.php/Category:Nucleotide_excision_repair nucleotide excision repair (NER)] <ref name="Lifuss">PMID: 18510924 </ref>. This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove the damaged DNA. <br /> <br /> Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP <ref name="Buechner">PMID: 24338567 </ref>. The ATP-dependent helicase activity of XPD helicase, however is only required for NER, even though TFIIH participates in both repair and transcription initiation <ref name="Kuper">PMID: 25268380 </ref>. XPD helicase not only unravels the DNA around the damage, but also helps TFIIH in recognizing bulky lesions in DNA <ref>DOI 10.1093/nar/gkw102 </ref>. The DNA is then threaded through the central pore of XPD helicase, which then opens up the double helix. <br /> <br /> == Disease ==<br /> The NER pathway consists of 28 genes, three of which are part of TFIIH, and mutations in many of these are associated with a set of diseases that are similar but have marked differences <ref name="Kraemer">PMID: 17276014 </ref>. Mutations in XPD helicase are associated with three distinct diseases: [https://ghr.nlm.nih.gov/condition/cockayne-syndrome Cockayne Syndrome (CS)], [https://ghr.nlm.nih.gov/condition/xeroderma-pigmentosum Xeroderma Pigmentosum (XP)], and [https://ghr.nlm.nih.gov/condition/trichothiodystrophy trichothiodystrophy (TTD)] <ref>DOI 10.1093/nar/gkv472</ref>. The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation <ref name="Lifuss">PMID: 18510924 </ref>.<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity <ref name="Nance">PMID: 1308368 </ref>. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer. Some XP patients have neurological degeneration, which can be explained by the fact that neurons do not divide, and mutations that are not corrected by NER could accumulate and eventually lead to cell death <ref name="Kraemer">PMID: 17276014 </ref>. TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity <ref name="Hashimoto">PMID: 19808800 </ref>. It has been proposed that specific mutations in XPD helicase affect the transcription activities of TFIIH more than its repair activities, resulting in development issues that lead to intellectual disabilities <ref name="Kraemer">PMID: 17276014 </ref>. Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. Different types of mutations in XPD helicase as well as interactions between XPD helicase mutations and defects in other NER proteins can result in these different diseases. Due to the complexity of these interactions, little is known about the molecular basis for the differences in these diseases <ref name="Kraemer">PMID: 17276014 </ref>. <br /> <br /> <br /> <br /> == References ==<br /> <references/></div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2588682 XPD Helicase (3CRV) 2016-04-27T21:01:46Z

<p>Bashir Noor: </p> <hr /> <div><StructureSection load='3CRV' size='450' side='right' scene='72/728075/Reset/2' caption='XPD helicase, 3CRV'><br /> <br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) helicase is a subunit of [http://proteopedia.org/wiki/index.php/Category:Tfiih Transcription Factor IIH (TFIIH)], which aids in [http://proteopedia.org/wiki/index.php/Category:Transcription_initiation transcription initiation] and DNA repair. XPD helicse unwinds DNA, allowing other [http://proteopedia.org/wiki/index.php/Category:Dna-repair DNA repair enzymes] to access and correct damaged regions in the DNA. XPD helicase helps to fix DNA damaged by ultraviolet (UV) light radiation, therefore mutations in XPD helicase results in diseases characterized by light sensitivity. <br /> <br /> == Structure ==<br /> XPD helicase's catalytic core (<scene name='72/728075/Domains/3'>Figure 1</scene>) is composed of four domains, HD1 (green), HD2 (red), 4FeS (brown), and Arch (blue) domains, and six motifs<ref name="Lifuss">PMID: 18510924 </ref>. The HD1 and HD2 domains form the ATP-Binding Interface.The 4FeS domain contains Cysteines 88, 102, 105, and 137 in which the Sulfur-Iron binding occurs (pink), the complex has the role of detecting DNA damage<ref name="Lifuss">PMID: 18510924 </ref>. ssDNA binding is facilitated by the 4FeS domain's Fe-S region and a channel is formed with HD1 and Arch Domains to form a passage way for the ssDNA <ref name="Lifuss">PMID: 18510924 </ref>. Positively charged residues along the channel are paired with negatively charged residues to allow subsequent ssDNA binding and movement along the ssDNA. HD2 domain and the Arch domain form the HD2 gateway which is associated with sensing bulky DNA damage as well<ref name="Lifuss">PMID: 18510924 </ref>. The motif's (<scene name='72/728075/Motifs/3'>Figure 2</scene>), I (31-60, red), II (177-186, blue), III (317-327, green), IV (394-408, brown), V (439-455, purple) and VI (501-517, orange), all play a role in both ATP and DNA binding<ref name="Lifuss">PMID: 18510924 </ref>. Motif's I, II, V, and VI all form the ATP binding site at the HD1 and HD2 interface (<scene name='72/728075/Atp_binding/2'>Figure 3</scene>)<ref name="Lifuss">PMID: 18510924 </ref>. Motif's IV, V, and VI within the HD2 domain form the gateway channel for DNA binding (<scene name='72/728075/Hd2_gate/2'>Figure 4</scene>)<ref name="Lifuss">PMID: 18510924 </ref>.<br /> (<scene name='72/728075/Reset/2'>Reset Molecule</scene>)<br /> <br /> == Function ==<br /> XPD helicase is an essential subunit of the general transcription factor IIH (TFIIH), which is a complex that, along with other general transcription factors, helps to initiate transcription and repair damaged DNA <ref name="Mydikova">PMID: 20429618</ref>. XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme <ref name="Lifuss">PMID: 18510924 </ref>. Helicases are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes, like polymerases, can act upon the DNA <ref name="Tuteja">PMID: 15128295 </ref>. In the context of DNA repair, helicases unwind DNA and other enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to UV radiation, adjacent nucleotide bases, often thymines, can react and form bulky pyrimidine dimers, which can block enzymes that work on DNA <ref name="Vink">PMID: 11809365 </ref>. For example, during DNA replication, [http://proteopedia.org/wiki/index.php/Category:Thymine_Dimers thymine dimers] do not fit into the active site of DNA polymerases smoothly, sometimes resulting in mismatched nucleotides. To fix this type of damage on single strands of DNA, cells employ a process called [http://proteopedia.org/wiki/index.php/Category:Nucleotide_excision_repair nucleotide excision repair (NER)] <ref name="Lifuss">PMID: 18510924 </ref>. This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove the damaged DNA. <br /> <br /> Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP <ref name="Buechner">PMID: 24338567 </ref>. The ATP-dependent helicase activity of XPD helicase, however is only required for NER, even though TFIIH participates in both repair and transcription initiation <ref name="Kuper">PMID: 25268380 </ref>. XPD helicase not only unravels the DNA around the damage, but also helps TFIIH in recognizing bulky lesions in DNA <ref>DOI 10.1093/nar/gkw102 </ref>. The DNA is then threaded through the central pore of XPD helicase, which then opens up the double helix. <br /> <br /> == Disease ==<br /> The NER pathway consists of 28 genes, three of which are part of TFIIH, and mutations in many of these are associated with a set of diseases that are similar but have marked differences <ref name="Kraemer">PMID: 17276014 </ref>. Mutations in XPD helicase are associated with three distinct diseases: [https://ghr.nlm.nih.gov/condition/cockayne-syndrome Cockayne Syndrome (CS)], [https://ghr.nlm.nih.gov/condition/xeroderma-pigmentosum Xeroderma Pigmentosum (XP)], and [https://ghr.nlm.nih.gov/condition/trichothiodystrophy trichothiodystrophy (TTD)] <ref>DOI 10.1093/nar/gkv472</ref>. The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation <ref name="Lifuss">PMID: 18510924 </ref>.<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity <ref name="Nance">PMID: 1308368 </ref>. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer. Some XP patients have neurological degeneration, which can be explained by the fact that neurons do not divide, and mutations that are not corrected by NER could accumulate and eventually lead to cell death <ref name="Kraemer">PMID: 17276014 </ref>. TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity <ref name="Hashimoto">PMID: 19808800 </ref>. It has been proposed that specific mutations in XPD helicase affect the transcription activities of TFIIH more than its repair activities, resulting in development issues that lead to intellectual disabilities <ref name="Kraemer">PMID: 17276014 </ref>. Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. Different types of mutations in XPD helicase as well as interactions between XPD helicase mutations and defects in other NER proteins can result in these different diseases. Due to the complexity of these interactions, little is known about the molecular basis for the differences in these diseases <ref name="Kraemer">PMID: 17276014 </ref>. <br /> <br /> <br /> <br /> == References ==<br /> <references/></div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2588673 XPD Helicase (3CRV) 2016-04-27T20:43:05Z

<p>Bashir Noor: </p> <hr /> <div><StructureSection load='3CRV' size='450' side='right' scene='72/728075/Reset/1' caption='XPD helicase, 3CRV'><br /> <br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) helicase is a subunit of [http://proteopedia.org/wiki/index.php/Category:Tfiih Transcription Factor IIH (TFIIH)], which aids in [http://proteopedia.org/wiki/index.php/Category:Transcription_initiation transcription initiation] and DNA repair. XPD helicse unwinds DNA, allowing other [http://proteopedia.org/wiki/index.php/Category:Dna-repair DNA repair enzymes] to access and correct damaged regions in the DNA. XPD helicase helps to fix DNA damaged by ultraviolet (UV) light radiation, therefore mutations in XPD helicase results in diseases characterized by light sensitivity. <br /> <br /> == Structure ==<br /> XPD helicase's catalytic core (<scene name='72/728075/Domains/2'>Figure 1</scene>) is composed of four domains, HD1 (green), HD2 (red), 4FeS (brown), and Arch (blue) domains, and six motifs. The HD1 and HD2 domains form the ATP-Binding Interface.The 4FeS domain contains Cysteines 88, 102, 105, and 137 in which the Sulfur-Iron binding occurs (pink), the complex has the role of detecting DNA damage. ssDNA binding is facilitated by the 4FeS domain's Fe-S region and a channel is formed with HD1 and Arch Domains to form a passage way for the ssDNA. Positively charged residues along the channel are paired with negatively charged residues to allow subsequent ssDNA binding and movement along the ssDNA. HD2 domain and the Arch domain form the HD2 gateway which is associated with sensing bulky DNA damage as well. The motif's (<scene name='72/728075/Motifs/2'>Figure 2</scene>), I (31-60, red), II (177-186, blue), III (317-327, green), IV (394-408, brown), V (439-455, purple) and VI (501-517, orange), all play a role in both ATP and DNA binding. Motif's I, II, V, and VI all form the ATP binding site at the HD1 and HD2 interface (<scene name='72/728075/Atp_binding/1'>Figure 3</scene>). Motif's IV, V, and VI within the HD2 domain form the gateway channel for DNA binding (<scene name='72/728075/Hd2_gate/1'>Figure 4</scene>). [http://www.omim.org/entry/601675 TTD1] <ref>DOI 10.1093/nar/gku989 </ref>. <br /> (<scene name='72/728075/Reset/1'>Reset</scene>)<br /> <br /> == Function ==<br /> XPD helicase is an essential subunit of the general transcription factor IIH (TFIIH), which is a complex that, along with other general transcription factors, helps to initiate transcription and repair damaged DNA <ref name="Mydikova">PMID: 20429618</ref>. XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme <ref name="Lifuss">PMID: 18510924 </ref>. Helicases are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes, like polymerases, can act upon the DNA <ref name="Tuteja">PMID: 15128295 </ref>. In the context of DNA repair, helicases unwind DNA and other enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to UV radiation, adjacent nucleotide bases, often thymines, can react and form bulky pyrimidine dimers, which can block enzymes that work on DNA <ref name="Vink">PMID: 11809365 </ref>. For example, during DNA replication, [http://proteopedia.org/wiki/index.php/Category:Thymine_Dimers thymine dimers] do not fit into the active site of DNA polymerases smoothly, sometimes resulting in mismatched nucleotides. To fix this type of damage on single strands of DNA, cells employ a process called [http://proteopedia.org/wiki/index.php/Category:Nucleotide_excision_repair nucleotide excision repair (NER)] <ref name="Lifuss">PMID: 18510924 </ref>. This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove the damaged DNA. <br /> <br /> Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP <ref name="Buechner">PMID: 24338567 </ref>. The ATP-dependent helicase activity of XPD helicase, however is only required for NER, even though TFIIH participates in both repair and transcription initiation <ref name="Kuper">PMID: 25268380 </ref>. XPD helicase not only unravels the DNA around the damage, but also helps TFIIH in recognizing bulky lesions in DNA <ref>DOI 10.1093/nar/gkw102 </ref>. The DNA is then threaded through the central pore of XPD helicase, which then opens up the double helix. <br /> <br /> == Disease ==<br /> The NER pathway consists of 28 genes, three of which are part of TFIIH, and mutations in many of these are associated with a set of diseases that are similar but have marked differences <ref name="Kraemer">PMID: 17276014 </ref>. Mutations in XPD helicase are associated with three distinct diseases: [https://ghr.nlm.nih.gov/condition/cockayne-syndrome Cockayne Syndrome (CS)], [https://ghr.nlm.nih.gov/condition/xeroderma-pigmentosum Xeroderma Pigmentosum (XP)], and [https://ghr.nlm.nih.gov/condition/trichothiodystrophy trichothiodystrophy (TTD)] <ref>DOI 10.1093/nar/gkv472</ref>. The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation <ref name="Lifuss">PMID: 18510924 </ref>.<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity <ref name="Nance">PMID: 1308368 </ref>. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer. Some XP patients have neurological degeneration, which can be explained by the fact that neurons do not divide, and mutations that are not corrected by NER could accumulate and eventually lead to cell death <ref name="Kraemer">PMID: 17276014 </ref>. TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity <ref name="Hashimoto">PMID: 19808800 </ref>. It has been proposed that specific mutations in XPD helicase affect the transcription activities of TFIIH more than its repair activities, resulting in development issues that lead to intellectual disabilities <ref name="Kraemer">PMID: 17276014 </ref>. Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. Different types of mutations in XPD helicase as well as interactions between XPD helicase mutations and defects in other NER proteins can result in these different diseases. Due to the complexity of these interactions, little is known about the molecular basis for the differences in these diseases <ref name="Kraemer">PMID: 17276014 </ref>. <br /> <br /> <br /> <br /> == References ==<br /> <references/></div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2588670 XPD Helicase (3CRV) 2016-04-27T20:41:06Z

<p>Bashir Noor: </p> <hr /> <div><StructureSection load='3CRV' size='450' side='right' scene='72/728075/Reset/1' caption='XPD helicase, 3CRV'><br /> <br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) helicase is a subunit of [http://proteopedia.org/wiki/index.php/Category:Tfiih Transcription Factor IIH (TFIIH)], which aids in [http://proteopedia.org/wiki/index.php/Category:Transcription_initiation transcription initiation] and DNA repair. XPD helicse unwinds DNA, allowing other [http://proteopedia.org/wiki/index.php/Category:Dna-repair DNA repair enzymes] to access and correct damaged regions in the DNA. XPD helicase helps to fix DNA damaged by ultraviolet (UV) light radiation, therefore mutations in XPD helicase results in diseases characterized by light sensitivity. <br /> <br /> == Function ==<br /> XPD helicase is an essential subunit of the general transcription factor IIH (TFIIH), which is a complex that, along with other general transcription factors, helps to initiate transcription and repair damaged DNA <ref name="Mydikova">PMID: 20429618</ref>. XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme <ref name="Lifuss">PMID: 18510924 </ref>. Helicases are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes, like polymerases, can act upon the DNA <ref name="Tuteja">PMID: 15128295 </ref>. In the context of DNA repair, helicases unwind DNA and other enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to UV radiation, adjacent nucleotide bases, often thymines, can react and form bulky pyrimidine dimers, which can block enzymes that work on DNA <ref name="Vink">PMID: 11809365 </ref>. For example, during DNA replication, [http://proteopedia.org/wiki/index.php/Category:Thymine_Dimers thymine dimers] do not fit into the active site of DNA polymerases smoothly, sometimes resulting in mismatched nucleotides. To fix this type of damage on single strands of DNA, cells employ a process called [http://proteopedia.org/wiki/index.php/Category:Nucleotide_excision_repair nucleotide excision repair (NER)] <ref name="Lifuss">PMID: 18510924 </ref>. This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove the damaged DNA. <br /> <br /> Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP <ref name="Buechner">PMID: 24338567 </ref>. The ATP-dependent helicase activity of XPD helicase, however is only required for NER, even though TFIIH participates in both repair and transcription initiation <ref name="Kuper">PMID: 25268380 </ref>. XPD helicase not only unravels the DNA around the damage, but also helps TFIIH in recognizing bulky lesions in DNA <ref>DOI 10.1093/nar/gkw102 </ref>. The DNA is then threaded through the central pore of XPD helicase, which then opens up the double helix. <br /> <br /> == Disease ==<br /> The NER pathway consists of 28 genes, three of which are part of TFIIH, and mutations in many of these are associated with a set of diseases that are similar but have marked differences <ref name="Kraemer">PMID: 17276014 </ref>. Mutations in XPD helicase are associated with three distinct diseases: [https://ghr.nlm.nih.gov/condition/cockayne-syndrome Cockayne Syndrome (CS)], [https://ghr.nlm.nih.gov/condition/xeroderma-pigmentosum Xeroderma Pigmentosum (XP)], and [https://ghr.nlm.nih.gov/condition/trichothiodystrophy trichothiodystrophy (TTD)] <ref>DOI 10.1093/nar/gkv472</ref>. The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation <ref name="Lifuss">PMID: 18510924 </ref>.<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity <ref name="Nance">PMID: 1308368 </ref>. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer. Some XP patients have neurological degeneration, which can be explained by the fact that neurons do not divide, and mutations that are not corrected by NER could accumulate and eventually lead to cell death <ref name="Kraemer">PMID: 17276014 </ref>. TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity <ref name="Hashimoto">PMID: 19808800 </ref>. It has been proposed that specific mutations in XPD helicase affect the transcription activities of TFIIH more than its repair activities, resulting in development issues that lead to intellectual disabilities <ref name="Kraemer">PMID: 17276014 </ref>. Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. Different types of mutations in XPD helicase as well as interactions between XPD helicase mutations and defects in other NER proteins can result in these different diseases. Due to the complexity of these interactions, little is known about the molecular basis for the differences in these diseases <ref name="Kraemer">PMID: 17276014 </ref>. <br /> <br /> == Structure ==<br /> XPD helicase's catalytic core (<scene name='72/728075/Domains/2'>Figure 1</scene>) is composed of four domains, HD1 (green), HD2 (red), 4FeS (brown), and Arch (blue) domains, and six motifs. The HD1 and HD2 domains form the ATP-Binding Interface.The 4FeS domain contains Cysteines 88, 102, 105, and 137 in which the Sulfur-Iron binding occurs (pink), the complex has the role of detecting DNA damage. ssDNA binding is facilitated by the 4FeS domain's Fe-S region and a channel is formed with HD1 and Arch Domains to form a passage way for the ssDNA. Positively charged residues along the channel are paired with negatively charged residues to allow subsequent ssDNA binding and movement along the ssDNA. HD2 domain and the Arch domain form the HD2 gateway which is associated with sensing bulky DNA damage as well. The motif's (<scene name='72/728075/Motifs/2'>Figure 2</scene>), I (31-60, red), II (177-186, blue), III (317-327, green), IV (394-408, brown), V (439-455, purple) and VI (501-517, orange), all play a role in both ATP and DNA binding. Motif's I, II, V, and VI all form the ATP binding site at the HD1 and HD2 interface (<scene name='72/728075/Atp_binding/1'>Figure 3</scene>). Motif's IV, V, and VI within the HD2 domain form the gateway channel for DNA binding (<scene name='72/728075/Hd2_gate/1'>Figure 4</scene>). [http://www.omim.org/entry/601675 TTD1] <ref>DOI 10.1093/nar/gku989 </ref>. <br /> (<scene name='72/728075/Reset/1'>Reset</scene>)<br /> <br /> <br /> <br /> <br /> <br /> == References ==<br /> <references/></div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2588666 XPD Helicase (3CRV) 2016-04-27T20:20:57Z

<p>Bashir Noor: </p> <hr /> <div><StructureSection load='3CRV' size='450' side='right' scene='72/728075/Reset/1' caption='XPD helicase, 3CRV'><br /> <br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) helicase is a subunit of [http://proteopedia.org/wiki/index.php/Category:Tfiih Transcription Factor IIH (TFIIH)], which aids in [http://proteopedia.org/wiki/index.php/Category:Transcription_initiation transcription initiation] and DNA repair. XPD helicse unwinds DNA, allowing other [http://proteopedia.org/wiki/index.php/Category:Dna-repair DNA repair enzymes] to access and correct damaged regions in the DNA. XPD helicase helps to fix DNA damaged by ultraviolet (UV) light radiation, therefore mutations in XPD helicase results in diseases characterized by light sensitivity. <br /> <br /> == Function ==<br /> XPD helicase is an essential subunit of the general transcription factor IIH (TFIIH), which is a complex that, along with other general transcription factors, helps to initiate transcription and repair damaged DNA <ref name="Mydikova">PMID: 20429618</ref>. XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme <ref name="Lifuss">PMID: 18510924 </ref>. Helicases are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes, like polymerases, can act upon the DNA <ref name="Tuteja">PMID: 15128295 </ref>. In the context of DNA repair, helicases unwind DNA and other enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to UV radiation, adjacent nucleotide bases, often thymines, can react and form bulky pyrimidine dimers, which can block enzymes that work on DNA <ref name="Vink">PMID: 11809365 </ref>. For example, during DNA replication, [http://proteopedia.org/wiki/index.php/Category:Thymine_Dimers thymine dimers] do not fit into the active site of DNA polymerases smoothly, sometimes resulting in mismatched nucleotides. To fix this type of damage on single strands of DNA, cells employ a process called [http://proteopedia.org/wiki/index.php/Category:Nucleotide_excision_repair nucleotide excision repair (NER)] <ref name="Lifuss">PMID: 18510924 </ref>. This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove the damaged DNA. <br /> <br /> Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP <ref name="Buechner">PMID: 24338567 </ref>. The ATP-dependent helicase activity of XPD helicase, however is only required for NER, even though TFIIH participates in both repair and transcription initiation <ref name="Kuper">PMID: 25268380 </ref>. XPD helicase not only unravels the DNA around the damage, but also helps TFIIH in recognizing bulky lesions in DNA <ref>DOI 10.1093/nar/gkw102 </ref>. The DNA is then threaded through the central pore of XPD helicase, which then opens up the double helix. <br /> <br /> == Disease ==<br /> The NER pathway consists of 28 genes, three of which are part of TFIIH, and mutations in many of these are associated with a set of diseases that are similar but have marked differences <ref name="Kraemer">PMID: 17276014 </ref>. Mutations in XPD helicase are associated with three distinct diseases: [https://ghr.nlm.nih.gov/condition/cockayne-syndrome Cockayne Syndrome (CS)], [https://ghr.nlm.nih.gov/condition/xeroderma-pigmentosum Xeroderma Pigmentosum (XP)], and [https://ghr.nlm.nih.gov/condition/trichothiodystrophy trichothiodystrophy (TTD)] <ref>DOI 10.1093/nar/gkv472</ref>. The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation <ref name="Lifuss">PMID: 18510924 </ref>.<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity <ref name="Nance">PMID: 1308368 </ref>. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer. Some XP patients have neurological degeneration, which can be explained by the fact that neurons do not divide, and mutations that are not corrected by NER could accumulate and eventually lead to cell death <ref name="Kraemer">PMID: 17276014 </ref>. TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity <ref name="Hashimoto">PMID: 19808800 </ref>. It has been proposed that specific mutations in XPD helicase affect the transcription activities of TFIIH more than its repair activities, resulting in development issues that lead to intellectual disabilities <ref name="Kraemer">PMID: 17276014 </ref>. Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. Different types of mutations in XPD helicase as well as interactions between XPD helicase mutations and defects in other NER proteins can result in these different diseases. Due to the complexity of these interactions, little is known about the molecular basis for the differences in these diseases <ref name="Kraemer">PMID: 17276014 </ref>. <br /> <br /> == Structure ==<br /> XPD helicase's catalytic core (<scene name='72/728075/Domains/2'>Figure 1</scene>) is composed of four domains, HD1, HD2, 4FeS, and Arch domains. HD1 (green) and HD2 (red) domains form the ATP-Binding Interface.The 4FeS domain (brown) contains Cysteines 88, 102, 105, and 137 in which the Sulfur-Iron binding occurs (pink), the complex has a large affinity for sensing DNA damage. ssDNA binding is facilitated by the 4FeS domain's Fe-S region and a channel is formed with HD1 and Arch Domains (blue) to form a passage way for the ssDNA. Positively charged residues along the channel are paired with negatively charged residues to allow subsequent ssDNA binding and movement along the ssDNA. HD2 domain and the Arch domain form the HD2 gateway which is associated with sensing bulky DNA damage as well. The motif's (<scene name='72/728075/Motifs/2'>Figure 2</scene>), I (31-60, red), II (177-186, blue), III (317-327, green), IV (394-408, brown), V (439-455, purple) and VI (501-517, orange), all play a role in both ATP and DNA binding. Motif's I, II, V, and VI all form the ATP binding site at the HD1 and HD2 interface (<scene name='72/728075/Atp_binding/1'>ATP-Binding</scene>). Motif's IV, V, and VI within the HD2 domain form the gateway for DNA binding. [http://www.omim.org/entry/601675 TTD1] <ref>DOI 10.1093/nar/gku989 </ref>. <br /> (<scene name='72/728075/Reset/1'>Reset</scene>)<br /> <br /> == Structural highlights ==<br /> <br /> <scene name='72/728075/Motifs/1'>Motifs</scene><br /> <br /> <scene name='72/728075/Domains/1'>Domains</scene><br /> <br /> <scene name='72/728075/Reset/1'>Reset</scene><br /> <br /> <br /> <br /> <br /> == References ==<br /> <references/></div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2588661 XPD Helicase (3CRV) 2016-04-27T20:10:06Z

<p>Bashir Noor: </p> <hr /> <div><StructureSection load='3CRV' size='450' side='right' scene='72/728075/Reset/1' caption='XPD helicase, 3CRV'><br /> <br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) helicase is a subunit of [http://proteopedia.org/wiki/index.php/Category:Tfiih Transcription Factor IIH (TFIIH)], which aids in [http://proteopedia.org/wiki/index.php/Category:Transcription_initiation transcription initiation] and DNA repair. XPD helicse unwinds DNA, allowing other [http://proteopedia.org/wiki/index.php/Category:Dna-repair DNA repair enzymes] to access and correct damaged regions in the DNA. XPD helicase helps to fix DNA damaged by ultraviolet (UV) light radiation, therefore mutations in XPD helicase results in diseases characterized by light sensitivity. <br /> <br /> == Function ==<br /> XPD helicase is an essential subunit of the general transcription factor IIH (TFIIH), which is a complex that, along with other general transcription factors, helps to initiate transcription and repair damaged DNA <ref name="Mydikova">PMID: 20429618</ref>. XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme <ref name="Lifuss">PMID: 18510924 </ref>. Helicases are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes, like polymerases, can act upon the DNA <ref name="Tuteja">PMID: 15128295 </ref>. In the context of DNA repair, helicases unwind DNA and other enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to UV radiation, adjacent nucleotide bases, often thymines, can react and form bulky pyrimidine dimers, which can block enzymes that work on DNA <ref name="Vink">PMID: 11809365 </ref>. For example, during DNA replication, [http://proteopedia.org/wiki/index.php/Category:Thymine_Dimers thymine dimers] do not fit into the active site of DNA polymerases smoothly, sometimes resulting in mismatched nucleotides. To fix this type of damage on single strands of DNA, cells employ a process called [http://proteopedia.org/wiki/index.php/Category:Nucleotide_excision_repair nucleotide excision repair (NER)] <ref name="Lifuss">PMID: 18510924 </ref>. This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove the damaged DNA. <br /> <br /> Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP <ref name="Buechner">PMID: 24338567 </ref>. The ATP-dependent helicase activity of XPD helicase, however is only required for NER, even though TFIIH participates in both repair and transcription initiation <ref name="Kuper">PMID: 25268380 </ref>. XPD helicase not only unravels the DNA around the damage, but also helps TFIIH in recognizing bulky lesions in DNA <ref>DOI 10.1093/nar/gkw102 </ref>. The DNA is then threaded through the central pore of XPD helicase, which then opens up the double helix. <br /> <br /> == Disease ==<br /> The NER pathway consists of 28 genes, three of which are part of TFIIH, and mutations in many of these are associated with a set of diseases that are similar but have marked differences <ref name="Kraemer">PMID: 17276014 </ref>. Mutations in XPD helicase are associated with three distinct diseases: [https://ghr.nlm.nih.gov/condition/cockayne-syndrome Cockayne Syndrome (CS)], [https://ghr.nlm.nih.gov/condition/xeroderma-pigmentosum Xeroderma Pigmentosum (XP)], and [https://ghr.nlm.nih.gov/condition/trichothiodystrophy trichothiodystrophy (TTD)] <ref>DOI 10.1093/nar/gkv472</ref>. The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation <ref name="Lifuss">PMID: 18510924 </ref>.<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity <ref name="Nance">PMID: 1308368 </ref>. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer. Some XP patients have neurological degeneration, which can be explained by the fact that neurons do not divide, and mutations that are not corrected by NER could accumulate and eventually lead to cell death <ref name="Kraemer">PMID: 17276014 </ref>. TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity <ref name="Hashimoto">PMID: 19808800 </ref>. It has been proposed that specific mutations in XPD helicase affect the transcription activities of TFIIH more than its repair activities, resulting in development issues that lead to intellectual disabilities <ref name="Kraemer">PMID: 17276014 </ref>. Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. Different types of mutations in XPD helicase as well as interactions between XPD helicase mutations and defects in other NER proteins can result in these different diseases. Due to the complexity of these interactions, little is known about the molecular basis for the differences in these diseases <ref name="Kraemer">PMID: 17276014 </ref>. <br /> <br /> == Structure ==<br /> XPD helicase's catalytic core (<scene name='72/728075/Domains/2'>Figure 1</scene>) is composed of four domains, HD1, HD2, 4FeS, and Arch domains. HD1 (green) and HD2 (red) domains form the ATP-Binding Interface.The 4FeS domain (brown) contains Cysteines 88, 102, 105, and 137 in which the Sulfur-Iron binding occurs (pink), the complex has a large affinity for sensing DNA damage. ssDNA binding is facilitated by the 4FeS domain's Fe-S region and a channel is formed with HD1 and Arch Domains (blue) to form a passage way for the ssDNA. Positively charged residues along the channel are paired with negatively charged residues to allow subsequent ssDNA binding and movement along the ssDNA. HD2 domain and the Arch domain form the HD2 gateway which is associated with sensing bulky DNA damage as well. The motif's (<scene name='72/728075/Motifs/2'>Figure 2</scene>), I (31-60, red), II (177-186, blue), III (317-327, green), IV (394-408, brown), V (439-455, purple) and IV (501-517, orange), all play a role in both ATP and DNA binding. Motif's I, II, V, and VI all form the ATP binding site at the HD1 and HD2 interface. Motif's IV, V, and VI within the HD2 domain form the gateway for DNA binding. [http://www.omim.org/entry/601675 TTD1] <ref>DOI 10.1093/nar/gku989 </ref>. <br /> (<scene name='72/728075/Reset/1'>Reset</scene>)<br /> <br /> == Structural highlights ==<br /> <br /> <scene name='72/728075/Motifs/1'>Motifs</scene><br /> <br /> <scene name='72/728075/Domains/1'>Domains</scene><br /> <br /> <scene name='72/728075/Reset/1'>Reset</scene><br /> <br /> <br /> <br /> <br /> == References ==<br /> <references/></div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2588649 XPD Helicase (3CRV) 2016-04-27T20:01:03Z

<p>Bashir Noor: </p> <hr /> <div><StructureSection load='3CRV' size='450' side='right' scene='72/728075/Reset/1' caption='XPD helicase, 3CRV'><br /> <br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) helicase is a subunit of [http://proteopedia.org/wiki/index.php/Category:Tfiih Transcription Factor IIH (TFIIH)], which aids in [http://proteopedia.org/wiki/index.php/Category:Transcription_initiation transcription initiation] and DNA repair. XPD helicse unwinds DNA, allowing other [http://proteopedia.org/wiki/index.php/Category:Dna-repair DNA repair enzymes] to access and correct damaged regions in the DNA. XPD helicase helps to fix DNA damaged by ultraviolet (UV) light radiation, therefore mutations in XPD helicase results in diseases characterized by light sensitivity. <br /> <br /> == Function ==<br /> XPD helicase is an essential subunit of the general transcription factor IIH (TFIIH), which is a complex that, along with other general transcription factors, helps to initiate transcription and repair damaged DNA <ref name="Mydikova">PMID: 20429618</ref>. XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme <ref name="Lifuss">PMID: 18510924 </ref>. Helicases are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes, like polymerases, can act upon the DNA <ref name="Tuteja">PMID: 15128295 </ref>. In the context of DNA repair, helicases unwind DNA and other enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to UV radiation, adjacent nucleotide bases, often thymines, can react and form bulky pyrimidine dimers, which can block enzymes that work on DNA <ref name="Vink">PMID: 11809365 </ref>. For example, during DNA replication, [http://proteopedia.org/wiki/index.php/Category:Thymine_Dimers thymine dimers] do not fit into the active site of DNA polymerases smoothly, sometimes resulting in mismatched nucleotides. To fix this type of damage on single strands of DNA, cells employ a process called [http://proteopedia.org/wiki/index.php/Category:Nucleotide_excision_repair nucleotide excision repair (NER)] <ref name="Lifuss">PMID: 18510924 </ref>. This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove the damaged DNA. <br /> <br /> Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP <ref name="Buechner">PMID: 24338567 </ref>. The ATP-dependent helicase activity of XPD helicase, however is only required for NER, even though TFIIH participates in both repair and transcription initiation <ref name="Kuper">PMID: 25268380 </ref>. XPD helicase not only unravels the DNA around the damage, but also helps TFIIH in recognizing bulky lesions in DNA <ref>DOI 10.1093/nar/gkw102 </ref>. The DNA is then threaded through the central pore of XPD helicase, which then opens up the double helix. <br /> <br /> == Disease ==<br /> The NER pathway consists of 28 genes, three of which are part of TFIIH, and mutations in many of these are associated with a set of diseases that are similar but have marked differences <ref name="Kraemer">PMID: 17276014 </ref>. Mutations in XPD helicase are associated with three distinct diseases: [https://ghr.nlm.nih.gov/condition/cockayne-syndrome Cockayne Syndrome (CS)], [https://ghr.nlm.nih.gov/condition/xeroderma-pigmentosum Xeroderma Pigmentosum (XP)], and [https://ghr.nlm.nih.gov/condition/trichothiodystrophy trichothiodystrophy (TTD)] <ref>DOI 10.1093/nar/gkv472</ref>. The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation <ref name="Lifuss">PMID: 18510924 </ref>.<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity <ref name="Nance">PMID: 1308368 </ref>. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer. Some XP patients have neurological degeneration, which can be explained by the fact that neurons do not divide, and mutations that are not corrected by NER could accumulate and eventually lead to cell death <ref name="Kraemer">PMID: 17276014 </ref>. TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity <ref name="Hashimoto">PMID: 19808800 </ref>. It has been proposed that specific mutations in XPD helicase affect the transcription activities of TFIIH more than its repair activities, resulting in development issues that lead to intellectual disabilities <ref name="Kraemer">PMID: 17276014 </ref>. Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. Different types of mutations in XPD helicase as well as interactions between XPD helicase mutations and defects in other NER proteins can result in these different diseases. Due to the complexity of these interactions, little is known about the molecular basis for the differences in these diseases <ref name="Kraemer">PMID: 17276014 </ref>. <br /> <br /> == Structure ==<br /> XPD helicase's catalytic core (<scene name='72/728075/Domains/2'>Figure 1</scene>) is composed of four domains, HD1, HD2, 4FeS, and Arch domains. HD1 (green) and HD2 (red) domains form the ATP-Binding Interface.The 4FeS domain (brown) contains Cysteines 88, 102, 105, and 137 in which the Sulfur-Iron binding occurs (pink), the complex has a large affinity for sensing DNA damage. ssDNA binding is facilitated by the 4FeS domain's Fe-S region and a channel is formed with HD1 and Arch Domains (blue) to form a passage way for the ssDNA. Positively charged residues along the channel are paired with negatively charged residues to allow subsequent ssDNA binding and movement along the ssDNA. HD2 domain and the Arch domain form the HD2 gateway which is associated with sensing bulky DNA damage as well. The motif's (<scene name='72/728075/Motifs/2'>Figure 2</scene>), I (31-60, red), II (177-186, blue), III (317-327, green), IV (394-408, brown), V (439-455, purple) and IV (501-517, orange), all play a . [http://www.omim.org/entry/601675 TTD1] <ref>DOI 10.1093/nar/gku989 </ref>. <br /> (<scene name='72/728075/Reset/1'>Reset</scene>)<br /> <br /> == Structural highlights ==<br /> <br /> <scene name='72/728075/Motifs/1'>Motifs</scene><br /> <br /> <scene name='72/728075/Domains/1'>Domains</scene><br /> <br /> <scene name='72/728075/Reset/1'>TextToBeDisplayed</scene><br /> <br /> <br /> <br /> <br /> == References ==<br /> <references/></div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2588648 XPD Helicase (3CRV) 2016-04-27T19:52:26Z

<p>Bashir Noor: </p> <hr /> <div><StructureSection load='3CRV' size='450' side='right' caption='XPD helicase, 3CRV'><br /> <br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) helicase is a subunit of [http://proteopedia.org/wiki/index.php/Category:Tfiih Transcription Factor IIH (TFIIH)], which aids in [http://proteopedia.org/wiki/index.php/Category:Transcription_initiation transcription initiation] and DNA repair. XPD helicse unwinds DNA, allowing other [http://proteopedia.org/wiki/index.php/Category:Dna-repair DNA repair enzymes] to access and correct damaged regions in the DNA. XPD helicase helps to fix DNA damaged by ultraviolet (UV) light radiation, therefore mutations in XPD helicase results in diseases characterized by light sensitivity. <br /> <br /> == Function ==<br /> XPD helicase is an essential subunit of the general transcription factor IIH (TFIIH), which is a complex that, along with other general transcription factors, helps to initiate transcription and repair damaged DNA <ref name="Mydikova">PMID: 20429618</ref>. XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme <ref name="Lifuss">PMID: 18510924 </ref>. Helicases are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes, like polymerases, can act upon the DNA <ref name="Tuteja">PMID: 15128295 </ref>. In the context of DNA repair, helicases unwind DNA and other enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to UV radiation, adjacent nucleotide bases, often thymines, can react and form bulky pyrimidine dimers, which can block enzymes that work on DNA <ref name="Vink">PMID: 11809365 </ref>. For example, during DNA replication, [http://proteopedia.org/wiki/index.php/Category:Thymine_Dimers thymine dimers] do not fit into the active site of DNA polymerases smoothly, sometimes resulting in mismatched nucleotides. To fix this type of damage on single strands of DNA, cells employ a process called [http://proteopedia.org/wiki/index.php/Category:Nucleotide_excision_repair nucleotide excision repair (NER)] <ref name="Lifuss">PMID: 18510924 </ref>. This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove the damaged DNA. <br /> <br /> Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP <ref name="Buechner">PMID: 24338567 </ref>. The ATP-dependent helicase activity of XPD helicase, however is only required for NER, even though TFIIH participates in both repair and transcription initiation <ref name="Kuper">PMID: 25268380 </ref>. XPD helicase not only unravels the DNA around the damage, but also helps TFIIH in recognizing bulky lesions in DNA <ref>DOI 10.1093/nar/gkw102 </ref>. The DNA is then threaded through the central pore of XPD helicase, which then opens up the double helix. <br /> <br /> == Disease ==<br /> The NER pathway consists of 28 genes, three of which are part of TFIIH, and mutations in many of these are associated with a set of diseases that are similar but have marked differences <ref name="Kraemer">PMID: 17276014 </ref>. Mutations in XPD helicase are associated with three distinct diseases: [https://ghr.nlm.nih.gov/condition/cockayne-syndrome Cockayne Syndrome (CS)], [https://ghr.nlm.nih.gov/condition/xeroderma-pigmentosum Xeroderma Pigmentosum (XP)], and [https://ghr.nlm.nih.gov/condition/trichothiodystrophy trichothiodystrophy (TTD)] <ref>DOI 10.1093/nar/gkv472</ref>. The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation <ref name="Lifuss">PMID: 18510924 </ref>.<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity <ref name="Nance">PMID: 1308368 </ref>. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer. Some XP patients have neurological degeneration, which can be explained by the fact that neurons do not divide, and mutations that are not corrected by NER could accumulate and eventually lead to cell death <ref name="Kraemer">PMID: 17276014 </ref>. TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity <ref name="Hashimoto">PMID: 19808800 </ref>. It has been proposed that specific mutations in XPD helicase affect the transcription activities of TFIIH more than its repair activities, resulting in development issues that lead to intellectual disabilities <ref name="Kraemer">PMID: 17276014 </ref>. Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. Different types of mutations in XPD helicase as well as interactions between XPD helicase mutations and defects in other NER proteins can result in these different diseases. Due to the complexity of these interactions, little is known about the molecular basis for the differences in these diseases <ref name="Kraemer">PMID: 17276014 </ref>. <br /> <br /> == Structure ==<br /> XPD helicase's catalytic core (<scene name='72/728075/Domains/2'>Figure 1</scene>) is composed of four domains, HD1, HD2, 4FeS, and Arch domains. HD1 (green) and HD2 (red) domains form the ATP-Binding Interface.The 4FeS domain (brown) contains Cysteines 88, 102, 105, and 137 in which the Sulfur-Iron binding occurs (pink), the complex has a large affinity for sensing DNA damage. ssDNA binding is facilitated by the 4FeS domain's Fe-S region and a channel is formed with HD1 and Arch Domains (blue) to form a passage way for the ssDNA. Positively charged residues along the channel are paired with negatively charged residues to allow subsequent ssDNA binding and movement along the ssDNA. HD2 domain and the Arch domain form the HD2 gateway which is associated with sensing bulky DNA damage as well. The motif's (<scene name='72/728075/Motifs/2'>Figure 2</scene>), I (31-60, red), II (177-186, blue), III (317-327, green), IV (394-408, brown), V (439-455, purple) and IV (501-517, orange), all play a . [http://www.omim.org/entry/601675 TTD1] <ref>DOI 10.1093/nar/gku989 </ref>. <br /> (<scene name='72/728075/Reset/1'>Reset</scene>)<br /> <br /> == Structural highlights ==<br /> <br /> <scene name='72/728075/Motifs/1'>Motifs</scene><br /> <br /> <scene name='72/728075/Domains/1'>Domains</scene><br /> <br /> <br /> <br /> <br /> == References ==<br /> <references/></div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2588646 XPD Helicase (3CRV) 2016-04-27T19:46:16Z

<p>Bashir Noor: </p> <hr /> <div><StructureSection load='3CRV' size='450' side='right' caption='XPD helicase, 3CRV'><br /> <br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) helicase is a subunit of [http://proteopedia.org/wiki/index.php/Category:Tfiih Transcription Factor IIH (TFIIH)], which aids in [http://proteopedia.org/wiki/index.php/Category:Transcription_initiation transcription initiation] and DNA repair. XPD helicse unwinds DNA, allowing other [http://proteopedia.org/wiki/index.php/Category:Dna-repair DNA repair enzymes] to access and correct damaged regions in the DNA. XPD helicase helps to fix DNA damaged by ultraviolet (UV) light radiation, therefore mutations in XPD helicase results in diseases characterized by light sensitivity. <br /> <br /> == Function ==<br /> XPD helicase is an essential subunit of the general transcription factor IIH (TFIIH), which is a complex that, along with other general transcription factors, helps to initiate transcription and repair damaged DNA <ref name="Mydikova">PMID: 20429618</ref>. XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme <ref name="Lifuss">PMID: 18510924 </ref>. Helicases are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes, like polymerases, can act upon the DNA <ref name="Tuteja">PMID: 15128295 </ref>. In the context of DNA repair, helicases unwind DNA and other enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to UV radiation, adjacent nucleotide bases, often thymines, can react and form bulky pyrimidine dimers, which can block enzymes that work on DNA <ref name="Vink">PMID: 11809365 </ref>. For example, during DNA replication, [http://proteopedia.org/wiki/index.php/Category:Thymine_Dimers thymine dimers] do not fit into the active site of DNA polymerases smoothly, sometimes resulting in mismatched nucleotides. To fix this type of damage on single strands of DNA, cells employ a process called [http://proteopedia.org/wiki/index.php/Category:Nucleotide_excision_repair nucleotide excision repair (NER)] <ref name="Lifuss">PMID: 18510924 </ref>. This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove the damaged DNA. <br /> <br /> Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP <ref name="Buechner">PMID: 24338567 </ref>. The ATP-dependent helicase activity of XPD helicase, however is only required for NER, even though TFIIH participates in both repair and transcription initiation <ref name="Kuper">PMID: 25268380 </ref>. XPD helicase not only unravels the DNA around the damage, but also helps TFIIH in recognizing bulky lesions in DNA <ref>DOI 10.1093/nar/gkw102 </ref>. The DNA is then threaded through the central pore of XPD helicase, which then opens up the double helix. <br /> <br /> == Disease ==<br /> The NER pathway consists of 28 genes, three of which are part of TFIIH, and mutations in many of these are associated with a set of diseases that are similar but have marked differences <ref name="Kraemer">PMID: 17276014 </ref>. Mutations in XPD helicase are associated with three distinct diseases: [https://ghr.nlm.nih.gov/condition/cockayne-syndrome Cockayne Syndrome (CS)], [https://ghr.nlm.nih.gov/condition/xeroderma-pigmentosum Xeroderma Pigmentosum (XP)], and [https://ghr.nlm.nih.gov/condition/trichothiodystrophy trichothiodystrophy (TTD)] <ref>DOI 10.1093/nar/gkv472</ref>. The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation <ref name="Lifuss">PMID: 18510924 </ref>.<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity <ref name="Nance">PMID: 1308368 </ref>. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer. Some XP patients have neurological degeneration, which can be explained by the fact that neurons do not divide, and mutations that are not corrected by NER could accumulate and eventually lead to cell death <ref name="Kraemer">PMID: 17276014 </ref>. TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity <ref name="Hashimoto">PMID: 19808800 </ref>. It has been proposed that specific mutations in XPD helicase affect the transcription activities of TFIIH more than its repair activities, resulting in development issues that lead to intellectual disabilities <ref name="Kraemer">PMID: 17276014 </ref>. Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. Different types of mutations in XPD helicase as well as interactions between XPD helicase mutations and defects in other NER proteins can result in these different diseases. Due to the complexity of these interactions, little is known about the molecular basis for the differences in these diseases <ref name="Kraemer">PMID: 17276014 </ref>. <br /> <br /> == Structure ==<br /> XPD helicase's catalytic core (<scene name='72/728075/Domains/2'>Figure 1</scene>) is composed of four domains, HD1, HD2, 4FeS, and Arch domains. HD1 (green) and HD2 (red) domains form the ATP-Binding Interface.The 4FeS domain (brown) contains Cysteines 88, 102, 105, and 137 in which the Sulfur-Iron binding occurs (pink), the complex has a large affinity for sensing DNA damage. ssDNA binding is facilitated by the 4FeS domain's Fe-S region and a channel is formed with HD1 and Arch Domains (blue) to form a passage way for the ssDNA. Positively charged residues along the channel are paired with negatively charged residues to allow subsequent ssDNA binding and movement along the ssDNA. HD2 domain and the Arch domain form the HD2 gateway which is associated with sensing bulky DNA damage as well. The motif's (<scene name='72/728075/Motifs/2'>Figure 2</scene>), I (31-60, red), II (177-186, blue), III (317-327, green), IV (394-408, brown), V (439-455, purple) and IV (501-517, orange), all play a . [http://www.omim.org/entry/601675 TTD1] <ref>DOI 10.1093/nar/gku989 </ref>. <br /> <br /> == Structural highlights ==<br /> <br /> <scene name='72/728075/Motifs/1'>Motifs</scene><br /> <br /> <scene name='72/728075/Domains/1'>Domains</scene><br /> <br /> <br /> <br /> <br /> == References ==<br /> <references/></div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2588626 XPD Helicase (3CRV) 2016-04-27T18:22:24Z

<p>Bashir Noor: </p> <hr /> <div><StructureSection load='3CRV' size='450' side='right' caption='XPD helicase, 3CRV'><br /> <br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) helicase is a subunit of [http://proteopedia.org/wiki/index.php/Category:Tfiih Transcription Factor IIH (TFIIH)], which aids in [http://proteopedia.org/wiki/index.php/Category:Transcription_initiation transcription initiation] and DNA repair. XPD helicse unwinds DNA, allowing other [http://proteopedia.org/wiki/index.php/Category:Dna-repair DNA repair enzymes] to access and correct damaged regions in the DNA. XPD helicase helps to fix DNA damaged by ultraviolet (UV) light radiation, therefore mutations in XPD helicase results in diseases characterized by light sensitivity. <br /> <br /> == Function ==<br /> XPD helicase is an essential subunit of the general transcription factor IIH (TFIIH), which is a complex that, along with other general transcription factors, helps to initiate transcription and repair damaged DNA <ref name="Mydikova">PMID: 20429618</ref>. XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme <ref name="Lifuss">PMID: 18510924 </ref>. Helicases are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes, like polymerases, can act upon the DNA <ref name="Tuteja">PMID: 15128295 </ref>. In the context of DNA repair, helicases unwind DNA and other enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to UV radiation, adjacent nucleotide bases, often thymines, can react and form bulky pyrimidine dimers, which can block enzymes that work on DNA <ref name="Vink">PMID: 11809365 </ref>. For example, during DNA replication, [http://proteopedia.org/wiki/index.php/Category:Thymine_Dimers thymine dimers] do not fit into the active site of DNA polymerases smoothly, sometimes resulting in mismatched nucleotides. To fix this type of damage on single strands of DNA, cells employ a process called [http://proteopedia.org/wiki/index.php/Category:Nucleotide_excision_repair nucleotide excision repair (NER)] <ref name="Lifuss">PMID: 18510924 </ref>. This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove the damaged DNA. <br /> <br /> Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP <ref name="Buechner">PMID: 24338567 </ref>. The ATP-dependent helicase activity of XPD helicase, however is only required for NER, even though TFIIH participates in both repair and transcription initiation <ref name="Kuper">PMID: 25268380 </ref>. XPD helicase not only unravels the DNA around the damage, but also helps TFIIH in recognizing bulky lesions in DNA <ref>DOI 10.1093/nar/gkw102 </ref>. The DNA is then threaded through the central pore of XPD helicase, which then opens up the double helix. <br /> <br /> == Disease ==<br /> The NER pathway consists of 28 genes, three of which are part of TFIIH, and mutations in many of these are associated with a set of diseases that are similar but have marked differences <ref name="Kraemer">PMID: 17276014 </ref>. Mutations in XPD helicase are associated with three distinct diseases: [https://ghr.nlm.nih.gov/condition/cockayne-syndrome Cockayne Syndrome (CS)], [https://ghr.nlm.nih.gov/condition/xeroderma-pigmentosum Xeroderma Pigmentosum (XP)], and [https://ghr.nlm.nih.gov/condition/trichothiodystrophy trichothiodystrophy (TTD)] <ref>DOI 10.1093/nar/gkv472</ref>. The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation <ref name="Lifuss">PMID: 18510924 </ref>.<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity <ref name="Nance">PMID: 1308368 </ref>. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer. Some XP patients have neurological degeneration, which can be explained by the fact that neurons do not divide, and mutations that are not corrected by NER could accumulate and eventually lead to cell death <ref name="Kraemer">PMID: 17276014 </ref>. TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity <ref name="Hashimoto">PMID: 19808800 </ref>. It has been proposed that specific mutations in XPD helicase affect the transcription activities of TFIIH more than its repair activities, resulting in development issues that lead to intellectual disabilities <ref name="Kraemer">PMID: 17276014 </ref>. Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. Different types of mutations in XPD helicase as well as interactions between XPD helicase mutations and defects in other NER proteins can result in these different diseases. Due to the complexity of these interactions, little is known about the molecular basis for the differences in these diseases <ref name="Kraemer">PMID: 17276014 </ref>. <br /> <br /> == Structure ==<br /> XPD helicase's catalytic core (<scene name='72/728075/Domains/1'>Domains</scene>) is composed of four domains, HD1, HD2, 4FeS, and Arch domains. HD1 (green) and HD2 (red) domains form the ATP-Binding Interface.The 4FeS domain (brown) contains Cysteines 88, 102, 105, and 137 in which the Sulfur-Iron binding occurs (pink), the complex has a large affinity for being oxidation. HD2 domain and the Arch domain (blue) form the HD2 gateway which is associated with sensing bulky DNA damage. The motif's (<scene name='72/728075/Motifs/2'>Motif</scene>), I (31-60, red), II (177-186, blue), III (317-327, green), IV (394-408, brown), V (439-455, purple) and IV (501-517, orange). [http://www.omim.org/entry/601675 TTD1] <ref>DOI 10.1093/nar/gku989 </ref>. <br /> <br /> == Structural highlights ==<br /> <br /> <scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene><br /> <br /> <scene name='72/728075/Nucleotide_binding/3'>ATP Binding</scene><br /> <br /> <scene name='72/728075/Deah_box/1'>DEAH Box</scene><br /> <br /> <scene name='72/728075/Iron_sulfur/1'>Iron Sulfur Binding</scene><br /> <br /> <scene name='72/728075/Motifs/1'>Motifs</scene><br /> <br /> <scene name='72/728075/Domains/1'>Domains</scene><br /> <br /> <br /> <br /> <br /> == References ==<br /> <references/></div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2588588 XPD Helicase (3CRV) 2016-04-27T03:40:00Z

<p>Bashir Noor: </p> <hr /> <div><StructureSection load='3CRV' size='450' side='right' caption='XPD helicase, 3CRV'><br /> <br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) helicase is a subunit of [http://proteopedia.org/wiki/index.php/Category:Tfiih Transcription Factor IIH (TFIIH)], which aids in [http://proteopedia.org/wiki/index.php/Category:Transcription_initiation transcription initiation] and DNA repair. XPD helicse unwinds DNA, allowing other [http://proteopedia.org/wiki/index.php/Category:Dna-repair DNA repair enzymes] to access and correct damaged regions in the DNA. XPD helicase helps to fix DNA damaged by ultraviolet (UV) light radiation, therefore mutations in XPD helicase results in diseases characterized by light sensitivity. <br /> <br /> == Function ==<br /> XPD helicase is an essential subunit of the general transcription factor IIH (TFIIH), which is a complex that, along with other general transcription factors, helps to initiate transcription and repair damaged DNA <ref name="Mydikova">PMID: 20429618</ref>. XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme <ref name="Lifuss">PMID: 18510924 </ref>. Helicases are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes, like polymerases, can act upon the DNA <ref name="Tuteja">PMID: 15128295 </ref>. In the context of DNA repair, helicases unwind DNA and other enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to UV radiation, adjacent nucleotide bases, often thymines, can react and form bulky pyrimidine dimers, which can block enzymes that work on DNA <ref name="Vink">PMID: 11809365 </ref>. For example, during DNA replication, [http://proteopedia.org/wiki/index.php/Category:Thymine_Dimers thymine dimers] do not fit into the active site of DNA polymerases smoothly, sometimes resulting in mismatched nucleotides. To fix this type of damage on single strands of DNA, cells employ a process called [http://proteopedia.org/wiki/index.php/Category:Nucleotide_excision_repair nucleotide excision repair (NER)] <ref name="Lifuss">PMID: 18510924 </ref>. This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove the damaged DNA. <br /> <br /> Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP <ref name="Buechner">PMID: 24338567 </ref>. The ATP-dependent helicase activity of XPD helicase, however is only required for NER, even though TFIIH participates in both repair and transcription initiation <ref name="Kuper">PMID: 25268380 </ref>. XPD helicase not only unravels the DNA around the damage, but also helps TFIIH in recognizing bulky lesions in DNA <ref>DOI 10.1093/nar/gkw102 </ref>. The DNA is then threaded through the central pore of XPD helicase, which then opens up the double helix. <br /> <br /> == Disease ==<br /> The NER pathway consists of 28 genes, three of which are part of TFIIH, and mutations in many of these are associated with a set of diseases that are similar but have marked differences <ref name="Kraemer">PMID: 17276014 </ref>. Mutations in XPD helicase are associated with three distinct diseases: [https://ghr.nlm.nih.gov/condition/cockayne-syndrome Cockayne Syndrome (CS)], [https://ghr.nlm.nih.gov/condition/xeroderma-pigmentosum Xeroderma Pigmentosum (XP)], and [https://ghr.nlm.nih.gov/condition/trichothiodystrophy trichothiodystrophy (TTD)] <ref>DOI 10.1093/nar/gkv472</ref>. The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation <ref name="Lifuss">PMID: 18510924 </ref>.<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity <ref name="Nance">PMID: 1308368 </ref>. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer. Some XP patients have neurological degeneration, which can be explained by the fact that neurons do not divide, and mutations that are not corrected by NER could accumulate and eventually lead to cell death <ref name="Kraemer">PMID: 17276014 </ref>. TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity <ref name="Hashimoto">PMID: 19808800 </ref>. It has been proposed that specific mutations in XPD helicase affect the transcription activities of TFIIH more than its repair activities, resulting in development issues that lead to intellectual disabilities <ref name="Kraemer">PMID: 17276014 </ref>. Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. Different types of mutations in XPD helicase as well as interactions between XPD helicase mutations and defects in other NER proteins can result in these different diseases. Due to the complexity of these interactions, little is known about the molecular basis for the differences in these diseases <ref name="Kraemer">PMID: 17276014 </ref>. <br /> <br /> == Structure ==<br /> XPD helicase's catalytic core (<scene name='72/728075/Domains/1'>Domains</scene>) is composed of four domains, HD1, HD2, 4FeS, and Arch domains. HD1 (green) and HD2 (red) domains form the ATP-Binding Interface.The 4FeS domain (brown) contains Cysteines 88, 102, 105, and 137 in which the Sulfur-Iron binding occurs (pink), the complex has a large affinity for being oxidation. HD2 domain and the Arch domain (blue) form the HD2 gateway which is associated with sensing bulky DNA damage. The motif's, I (31-60, red), II (177-186, blue), III (317-327, green), IV (394-408, brown), V (439-455, purple) and IV (501-517, orange). [http://www.omim.org/entry/601675 TTD1] <ref>DOI 10.1093/nar/gku989 </ref>. <br /> <br /> == Structural highlights ==<br /> <br /> <scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene><br /> <br /> <scene name='72/728075/Nucleotide_binding/3'>ATP Binding</scene><br /> <br /> <scene name='72/728075/Deah_box/1'>DEAH Box</scene><br /> <br /> <scene name='72/728075/Iron_sulfur/1'>Iron Sulfur Binding</scene><br /> <br /> <scene name='72/728075/Motifs/1'>Motifs</scene><br /> <br /> <scene name='72/728075/Domains/1'>Domains</scene><br /> <br /> <br /> <br /> <br /> == References ==<br /> <references/></div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2588586 XPD Helicase (3CRV) 2016-04-27T03:30:37Z

<p>Bashir Noor: </p> <hr /> <div><StructureSection load='3CRV' size='450' side='right' caption='XPD helicase, 3CRV'><br /> <br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) helicase is a subunit of [http://proteopedia.org/wiki/index.php/Category:Tfiih Transcription Factor IIH (TFIIH)], which aids in [http://proteopedia.org/wiki/index.php/Category:Transcription_initiation transcription initiation] and DNA repair. XPD helicse unwinds DNA, allowing other [http://proteopedia.org/wiki/index.php/Category:Dna-repair DNA repair enzymes] to access and correct damaged regions in the DNA. XPD helicase helps to fix DNA damaged by ultraviolet (UV) light radiation, therefore mutations in XPD helicase results in diseases characterized by light sensitivity. <br /> <br /> == Function ==<br /> XPD helicase is an essential subunit of the general transcription factor IIH (TFIIH), which is a complex that, along with other general transcription factors, helps to initiate transcription and repair damaged DNA <ref name="Mydikova">PMID: 20429618</ref>. XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme <ref name="Lifuss">PMID: 18510924 </ref>. Helicases are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes, like polymerases, can act upon the DNA <ref name="Tuteja">PMID: 15128295 </ref>. In the context of DNA repair, helicases unwind DNA and other enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to UV radiation, adjacent nucleotide bases, often thymines, can react and form bulky pyrimidine dimers, which can block enzymes that work on DNA <ref name="Vink">PMID: 11809365 </ref>. For example, during DNA replication, [http://proteopedia.org/wiki/index.php/Category:Thymine_Dimers thymine dimers] do not fit into the active site of DNA polymerases smoothly, sometimes resulting in mismatched nucleotides. To fix this type of damage on single strands of DNA, cells employ a process called [http://proteopedia.org/wiki/index.php/Category:Nucleotide_excision_repair nucleotide excision repair (NER)] <ref name="Lifuss">PMID: 18510924 </ref>. This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove the damaged DNA. <br /> <br /> Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP <ref name="Buechner">PMID: 24338567 </ref>. The ATP-dependent helicase activity of XPD helicase, however is only required for NER, even though TFIIH participates in both repair and transcription initiation <ref name="Kuper">PMID: 25268380 </ref>. XPD helicase not only unravels the DNA around the damage, but also helps TFIIH in recognizing bulky lesions in DNA <ref>DOI 10.1093/nar/gkw102 </ref>. The DNA is then threaded through the central pore of XPD helicase, which then opens up the double helix. <br /> <br /> == Disease ==<br /> The NER pathway consists of 28 genes, three of which are part of TFIIH, and mutations in many of these are associated with a set of diseases that are similar but have marked differences <ref name="Kraemer">PMID: 17276014 </ref>. Mutations in XPD helicase are associated with three distinct diseases: [https://ghr.nlm.nih.gov/condition/cockayne-syndrome Cockayne Syndrome (CS)], [https://ghr.nlm.nih.gov/condition/xeroderma-pigmentosum Xeroderma Pigmentosum (XP)], and [https://ghr.nlm.nih.gov/condition/trichothiodystrophy trichothiodystrophy (TTD)] <ref>DOI 10.1093/nar/gkv472</ref>. The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation <ref name="Lifuss">PMID: 18510924 </ref>.<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity <ref name="Nance">PMID: 1308368 </ref>. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer. Some XP patients have neurological degeneration, which can be explained by the fact that neurons do not divide, and mutations that are not corrected by NER could accumulate and eventually lead to cell death <ref name="Kraemer">PMID: 17276014 </ref>. TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity <ref name="Hashimoto">PMID: 19808800 </ref>. It has been proposed that specific mutations in XPD helicase affect the transcription activities of TFIIH more than its repair activities, resulting in development issues that lead to intellectual disabilities <ref name="Kraemer">PMID: 17276014 </ref>. Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. Different types of mutations in XPD helicase as well as interactions between XPD helicase mutations and defects in other NER proteins can result in these different diseases. Due to the complexity of these interactions, little is known about the molecular basis for the differences in these diseases <ref name="Kraemer">PMID: 17276014 </ref>. <br /> <br /> == Structure ==<br /> XPD helicase's catalytic core (<scene name='72/728075/Domains/1'>Domains</scene>) is composed of four domains, HD1, HD2, 4FeS, and Arch domains. HD1 (green) and HD2 (red) domains form the ATP-Binding Interface.The 4FeS domain (brown) contains Cysteines 88, 102, 105, and 137 in which the Sulfur-Iron binding occurs (pink), the complex has a large affinity for being oxidation. HD2 domain and the Arch domain (blue) form the HD2 gateway which is associated with sensing bulky DNA damage. The motif's I (31-60), II (177-186), III (317-327), IV (394-408), V (439-455) and IV (501-517). [http://www.omim.org/entry/601675 TTD1] <ref>DOI 10.1093/nar/gku989 </ref>. <br /> <br /> == Structural highlights ==<br /> <br /> <scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene><br /> <br /> <scene name='72/728075/Nucleotide_binding/3'>ATP Binding</scene><br /> <br /> <scene name='72/728075/Deah_box/1'>DEAH Box</scene><br /> <br /> <scene name='72/728075/Iron_sulfur/1'>Iron Sulfur Binding</scene><br /> <br /> <scene name='72/728075/Motifs/1'>Motifs</scene><br /> <br /> <scene name='72/728075/Domains/1'>Domains</scene><br /> <br /> <br /> <br /> <br /> == References ==<br /> <references/></div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2588583 XPD Helicase (3CRV) 2016-04-27T03:15:36Z

<p>Bashir Noor: </p> <hr /> <div><StructureSection load='3CRV' size='450' side='right' caption='XPD helicase, 3CRV'><br /> <br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) helicase is a subunit of [http://proteopedia.org/wiki/index.php/Category:Tfiih Transcription Factor IIH (TFIIH)], which aids in [http://proteopedia.org/wiki/index.php/Category:Transcription_initiation transcription initiation] and DNA repair. XPD helicse unwinds DNA, allowing other [http://proteopedia.org/wiki/index.php/Category:Dna-repair DNA repair enzymes] to access and correct damaged regions in the DNA. XPD helicase helps to fix DNA damaged by ultraviolet (UV) light radiation, therefore mutations in XPD helicase results in diseases characterized by light sensitivity. <br /> <br /> == Function ==<br /> XPD helicase is an essential subunit of the general transcription factor IIH (TFIIH), which is a complex that, along with other general transcription factors, helps to initiate transcription and repair damaged DNA <ref name="Mydikova">PMID: 20429618</ref>. XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme <ref name="Lifuss">PMID: 18510924 </ref>. Helicases are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes, like polymerases, can act upon the DNA <ref name="Tuteja">PMID: 15128295 </ref>. In the context of DNA repair, helicases unwind DNA and other enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to UV radiation, adjacent nucleotide bases, often thymines, can react and form bulky pyrimidine dimers, which can block enzymes that work on DNA <ref name="Vink">PMID: 11809365 </ref>. For example, during DNA replication, [http://proteopedia.org/wiki/index.php/Category:Thymine_Dimers thymine dimers] do not fit into the active site of DNA polymerases smoothly, sometimes resulting in mismatched nucleotides. To fix this type of damage on single strands of DNA, cells employ a process called [http://proteopedia.org/wiki/index.php/Category:Nucleotide_excision_repair nucleotide excision repair (NER)] <ref name="Lifuss">PMID: 18510924 </ref>. This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove the damaged DNA. <br /> <br /> Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP <ref name="Buechner">PMID: 24338567 </ref>. The ATP-dependent helicase activity of XPD helicase, however is only required for NER, even though TFIIH participates in both repair and transcription initiation <ref name="Kuper">PMID: 25268380 </ref>. XPD helicase not only unravels the DNA around the damage, but also helps TFIIH in recognizing bulky lesions in DNA <ref>DOI 10.1093/nar/gkw102 </ref>. The DNA is then threaded through the central pore of XPD helicase, which then opens up the double helix. <br /> <br /> == Disease ==<br /> The NER pathway consists of 28 genes, three of which are part of TFIIH, and mutations in many of these are associated with a set of diseases that are similar but have marked differences <ref name="Kraemer">PMID: 17276014 </ref>. Mutations in XPD helicase are associated with three distinct diseases: [https://ghr.nlm.nih.gov/condition/cockayne-syndrome Cockayne Syndrome (CS)], [https://ghr.nlm.nih.gov/condition/xeroderma-pigmentosum Xeroderma Pigmentosum (XP)], and [https://ghr.nlm.nih.gov/condition/trichothiodystrophy trichothiodystrophy (TTD)] <ref>DOI 10.1093/nar/gkv472</ref>. The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation <ref name="Lifuss">PMID: 18510924 </ref>.<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity <ref name="Nance">PMID: 1308368 </ref>. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer. Some XP patients have neurological degeneration, which can be explained by the fact that neurons do not divide, and mutations that are not corrected by NER could accumulate and eventually lead to cell death <ref name="Kraemer">PMID: 17276014 </ref>. TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity <ref name="Hashimoto">PMID: 19808800 </ref>. It has been proposed that specific mutations in XPD helicase affect the transcription activities of TFIIH more than its repair activities, resulting in development issues that lead to intellectual disabilities <ref name="Kraemer">PMID: 17276014 </ref>. Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. Different types of mutations in XPD helicase as well as interactions between XPD helicase mutations and defects in other NER proteins can result in these different diseases. Due to the complexity of these interactions, little is known about the molecular basis for the differences in these diseases <ref name="Kraemer">PMID: 17276014 </ref>. <br /> <br /> == Structure ==<br /> XPD helicase's catalytic core is composed of four domains, HD1, HD2, 4FeS, and Arch domains. HD1 (green) and HD2 (red) domains form the ATP-Binding Interface.The 4FeS domain (brown) contains Cysteines 88, 102, 105, and 137 in which the Sulfur-Iron binding occurs (pink), the complex has a large affinity for oxidation. HD2 domain and the Arch domain (blue) form the HD2 gateway which is associated with sensing bulky DNA damage. [http://www.omim.org/entry/601675 TTD1] <ref>DOI 10.1093/nar/gku989 </ref>. <br /> <br /> == Structural highlights ==<br /> <br /> <scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene><br /> <br /> <scene name='72/728075/Nucleotide_binding/3'>ATP Binding</scene><br /> <br /> <scene name='72/728075/Deah_box/1'>DEAH Box</scene><br /> <br /> <scene name='72/728075/Iron_sulfur/1'>Iron Sulfur Binding</scene><br /> <br /> <scene name='72/728075/Motifs/1'>Motifs</scene><br /> <br /> <scene name='72/728075/Domains/1'>Domains</scene><br /> <br /> <br /> <br /> <br /> == References ==<br /> <references/></div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2588573 XPD Helicase (3CRV) 2016-04-27T02:06:21Z

<p>Bashir Noor: </p> <hr /> <div><StructureSection load='3CRV' size='450' side='right' caption='XPD helicase, 3CRV'><br /> <br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) helicase is a subunit of [http://proteopedia.org/wiki/index.php/Category:Tfiih Transcription Factor IIH (TFIIH)], which aids in [http://proteopedia.org/wiki/index.php/Category:Transcription_initiation transcription initiation] and DNA repair. XPD helicse unwinds DNA, allowing other [http://proteopedia.org/wiki/index.php/Category:Dna-repair DNA repair enzymes] to access and correct damaged regions in the DNA. XPD helicase helps to fix DNA damaged by ultraviolet (UV) light radiation, therefore mutations in XPD helicase results in diseases characterized by light sensitivity. <br /> <br /> == Function ==<br /> XPD helicase is an essential subunit of the general transcription factor IIH (TFIIH), which is a complex that, along with other general transcription factors, helps to initiate transcription and repair damaged DNA <ref name="Mydikova">PMID: 20429618</ref>. XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme <ref name="Lifuss">PMID: 18510924 </ref>. Helicases are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes, like polymerases, can act upon the DNA <ref name="Tuteja">PMID: 15128295 </ref>. In the context of DNA repair, helicases unwind DNA and other enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to UV radiation, adjacent nucleotide bases, often thymines, can react and form bulky pyrimidine dimers, which can block enzymes that work on DNA <ref name="Vink">PMID: 11809365 </ref>. For example, during DNA replication, [http://proteopedia.org/wiki/index.php/Category:Thymine_Dimers thymine dimers] do not fit into the active site of DNA polymerases smoothly, sometimes resulting in mismatched nucleotides. To fix this type of damage on single strands of DNA, cells employ a process called [http://proteopedia.org/wiki/index.php/Category:Nucleotide_excision_repair nucleotide excision repair (NER)] <ref name="Lifuss">PMID: 18510924 </ref>. This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove the damaged DNA. <br /> <br /> Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP <ref name="Buechner">PMID: 24338567 </ref>. The ATP-dependent helicase activity of XPD helicase, however is only required for NER, even though TFIIH participates in both repair and transcription initiation <ref name="Kuper">PMID: 25268380 </ref>. XPD helicase not only unravels the DNA around the damage, but also helps TFIIH in recognizing bulky lesions in DNA <ref>DOI 10.1093/nar/gkw102 </ref>. The DNA is then threaded through the central pore of XPD helicase, which then opens up the double helix. <br /> <br /> == Disease ==<br /> The NER pathway consists of 28 genes, three of which are part of TFIIH, and mutations in many of these are associated with a set of diseases that are similar but have marked differences <ref name="Kraemer">PMID: 17276014 </ref>. Mutations in XPD helicase are associated with three distinct diseases: [https://ghr.nlm.nih.gov/condition/cockayne-syndrome Cockayne Syndrome (CS)], [https://ghr.nlm.nih.gov/condition/xeroderma-pigmentosum Xeroderma Pigmentosum (XP)], and [https://ghr.nlm.nih.gov/condition/trichothiodystrophy trichothiodystrophy (TTD)] <ref>DOI 10.1093/nar/gkv472</ref>. The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation <ref name="Lifuss">PMID: 18510924 </ref>.<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity <ref name="Nance">PMID: 1308368 </ref>. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer. Some XP patients have neurological degeneration, which can be explained by the fact that neurons do not divide, and mutations that are not corrected by NER could accumulate and eventually lead to cell death <ref name="Kraemer">PMID: 17276014 </ref>. TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity <ref name="Hashimoto">PMID: 19808800 </ref>. It has been proposed that specific mutations in XPD helicase affect the transcription activities of TFIIH more than its repair activities, resulting in development issues that lead to intellectual disabilities <ref name="Kraemer">PMID: 17276014 </ref>. Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. Different types of mutations in XPD helicase as well as interactions between XPD helicase mutations and defects in other NER proteins can result in these different diseases. Due to the complexity of these interactions, little is known about the molecular basis for the differences in these diseases <ref name="Kraemer">PMID: 17276014 </ref>. <br /> <br /> == Structure ==<br /> XPD helicase's catalytic core is composed of four domains, HD1, HD2, 4FeS, and Arch domains. Residues 7-283 form the Helicase ATP binding domain(<scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene>), where ATP itself binds at residues 42-49, (<scene name='72/728075/Nucleotide_binding/4'>ATP Binding</scene>). Interaction with the gene MMS19 is mediated by region consisting of residues 438-637. Residues 234-237 form the motif which is the DEAH box of this transcription factor which is where the unwinding of DNA is performed (<scene name='72/728075/Deah_box/1'>DEAH Box</scene>). Iron Sulfur bonding residues consist of C116, C134, C155, and C160,(<scene name='72/728075/Iron_sulfur/2'>Iron Sulfur Binding</scene>). Features of Cockayne Syndrome and Xeroderma pigmentosum have been associated with the point mutation G602D, and the point mutation L461V is associated with [http://www.omim.org/entry/601675 TTD1] <ref>DOI 10.1093/nar/gku989 </ref>. <br /> <br /> == Structural highlights ==<br /> <br /> <scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene><br /> <br /> <scene name='72/728075/Nucleotide_binding/3'>ATP Binding</scene><br /> <br /> <scene name='72/728075/Deah_box/1'>DEAH Box</scene><br /> <br /> <scene name='72/728075/Iron_sulfur/1'>Iron Sulfur Binding</scene><br /> <br /> <scene name='72/728075/Motifs/1'>Motifs</scene><br /> <br /> <scene name='72/728075/Domains/1'>Domains</scene><br /> <br /> <br /> <br /> <br /> == References ==<br /> <references/></div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2588569 XPD Helicase (3CRV) 2016-04-27T01:42:25Z

<p>Bashir Noor: </p> <hr /> <div><StructureSection load='3CRV' size='450' side='right' caption='XPD helicase, 3CRV'><br /> <br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) helicase is a subunit of [http://proteopedia.org/wiki/index.php/Category:Tfiih Transcription Factor IIH (TFIIH)], which aids in [http://proteopedia.org/wiki/index.php/Category:Transcription_initiation transcription initiation] and DNA repair. XPD helicse unwinds DNA, allowing other [http://proteopedia.org/wiki/index.php/Category:Dna-repair DNA repair enzymes] to access and correct damaged regions in the DNA. XPD helicase helps to fix DNA damaged by ultraviolet (UV) light radiation, therefore mutations in XPD helicase results in diseases characterized by light sensitivity. <br /> <br /> == Function ==<br /> XPD helicase is an essential subunit of the general transcription factor IIH (TFIIH), which is a complex that, along with other general transcription factors, helps to initiate transcription and repair damaged DNA <ref name="Mydikova">PMID: 20429618</ref>. XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme <ref name="Lifuss">PMID: 18510924 </ref>. Helicases are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes, like polymerases, can act upon the DNA <ref name="Tuteja">PMID: 15128295 </ref>. In the context of DNA repair, helicases unwind DNA and other enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to UV radiation, adjacent nucleotide bases, often thymines, can react and form bulky pyrimidine dimers, which can block enzymes that work on DNA <ref name="Vink">PMID: 11809365 </ref>. For example, during DNA replication, [http://proteopedia.org/wiki/index.php/Category:Thymine_Dimers thymine dimers] do not fit into the active site of DNA polymerases smoothly, sometimes resulting in mismatched nucleotides. To fix this type of damage on single strands of DNA, cells employ a process called [http://proteopedia.org/wiki/index.php/Category:Nucleotide_excision_repair nucleotide excision repair (NER)] <ref name="Lifuss">PMID: 18510924 </ref>. This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove the damaged DNA. <br /> <br /> Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP <ref name="Buechner">PMID: 24338567 </ref>. The ATP-dependent helicase activity of XPD helicase, however is only required for NER, even though TFIIH participates in both repair and transcription initiation <ref name="Kuper">PMID: 25268380 </ref>. XPD helicase not only unravels the DNA around the damage, but also helps TFIIH in recognizing bulky lesions in DNA <ref>DOI 10.1093/nar/gkw102 </ref>. The DNA is then threaded through the central pore of XPD helicase, which then opens up the double helix. <br /> <br /> == Disease ==<br /> The NER pathway consists of 28 genes, three of which are part of TFIIH, and mutations in many of these are associated with a set of diseases that are similar but have marked differences <ref name="Kraemer">PMID: 17276014 </ref>. Mutations in XPD helicase are associated with three distinct diseases: [https://ghr.nlm.nih.gov/condition/cockayne-syndrome Cockayne Syndrome (CS)], [https://ghr.nlm.nih.gov/condition/xeroderma-pigmentosum Xeroderma Pigmentosum (XP)], and [https://ghr.nlm.nih.gov/condition/trichothiodystrophy trichothiodystrophy (TTD)] <ref>DOI 10.1093/nar/gkv472</ref>. The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation <ref name="Lifuss">PMID: 18510924 </ref>.<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity <ref name="Nance">PMID: 1308368 </ref>. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer. Some XP patients have neurological degeneration, which can be explained by the fact that neurons do not divide, and mutations that are not corrected by NER could accumulate and eventually lead to cell death <ref name="Kraemer">PMID: 17276014 </ref>. TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity <ref name="Hashimoto">PMID: 19808800 </ref>. It has been proposed that specific mutations in XPD helicase affect the transcription activities of TFIIH more than its repair activities, resulting in development issues that lead to intellectual disabilities <ref name="Kraemer">PMID: 17276014 </ref>. Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. Different types of mutations in XPD helicase as well as interactions between XPD helicase mutations and defects in other NER proteins can result in these different diseases. Due to the complexity of these interactions, little is known about the molecular basis for the differences in these diseases <ref name="Kraemer">PMID: 17276014 </ref>. <br /> <br /> == Structure ==<br /> XPD helicase's catalytic core is composed of four domains, HD1, HD2, 4FeS, and Arch domains. Residues 7-283 form the Helicase ATP binding domain(<scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene>), where ATP itself binds at residues 42-49, (<scene name='72/728075/Nucleotide_binding/4'>ATP Binding</scene>). Interaction with the gene MMS19 is mediated by region consisting of residues 438-637. Residues 234-237 form the motif which is the DEAH box of this transcription factor which is where the unwinding of DNA is performed (<scene name='72/728075/Deah_box/1'>DEAH Box</scene>). Iron Sulfur bonding residues consist of C116, C134, C155, and C160,(<scene name='72/728075/Iron_sulfur/2'>Iron Sulfur Binding</scene>). Features of Cockayne Syndrome and Xeroderma pigmentosum have been associated with the point mutation G602D, and the point mutation L461V is associated with [http://www.omim.org/entry/601675 TTD1] <ref>DOI 10.1093/nar/gku989 </ref>. <br /> <br /> == Structural highlights ==<br /> <br /> <scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene><br /> <br /> <scene name='72/728075/Nucleotide_binding/3'>ATP Binding</scene><br /> <br /> <scene name='72/728075/Deah_box/1'>DEAH Box</scene><br /> <br /> <scene name='72/728075/Iron_sulfur/1'>Iron Sulfur Binding</scene><br /> <br /> <scene name='72/728075/Arch_domain/1'>Arch Domain</scene><br /> <br /> <scene name='72/728075/Domains/1'>Domains</scene><br /> <br /> <br /> <br /> <br /> == References ==<br /> <references/></div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2588568 XPD Helicase (3CRV) 2016-04-27T01:26:11Z

<p>Bashir Noor: </p> <hr /> <div><StructureSection load='3CRV' size='450' side='right' caption='XPD helicase, 3CRV'><br /> <br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) helicase is a subunit of [http://proteopedia.org/wiki/index.php/Category:Tfiih Transcription Factor IIH (TFIIH)], which aids in [http://proteopedia.org/wiki/index.php/Category:Transcription_initiation transcription initiation] and DNA repair. XPD helicse unwinds DNA, allowing other [http://proteopedia.org/wiki/index.php/Category:Dna-repair DNA repair enzymes] to access and correct damaged regions in the DNA. XPD helicase helps to fix DNA damaged by ultraviolet (UV) light radiation, therefore mutations in XPD helicase results in diseases characterized by light sensitivity. <br /> <br /> == Function ==<br /> XPD helicase is an essential subunit of the general transcription factor IIH (TFIIH), which is a complex that, along with other general transcription factors, helps to initiate transcription and repair damaged DNA <ref name="Mydikova">PMID: 20429618</ref>. XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme <ref name="Lifuss">PMID: 18510924 </ref>. Helicases are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes, like polymerases, can act upon the DNA <ref name="Tuteja">PMID: 15128295 </ref>. In the context of DNA repair, helicases unwind DNA and other enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to UV radiation, adjacent nucleotide bases, often thymines, can react and form bulky pyrimidine dimers, which can block enzymes that work on DNA <ref name="Vink">PMID: 11809365 </ref>. For example, during DNA replication, [http://proteopedia.org/wiki/index.php/Category:Thymine_Dimers thymine dimers] do not fit into the active site of DNA polymerases smoothly, sometimes resulting in mismatched nucleotides. To fix this type of damage on single strands of DNA, cells employ a process called [http://proteopedia.org/wiki/index.php/Category:Nucleotide_excision_repair nucleotide excision repair (NER)] <ref name="Lifuss">PMID: 18510924 </ref>. This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove the damaged DNA. <br /> <br /> Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP <ref name="Buechner">PMID: 24338567 </ref>. The ATP-dependent helicase activity of XPD helicase, however is only required for NER, even though TFIIH participates in both repair and transcription initiation <ref name="Kuper">PMID: 25268380 </ref>. XPD helicase not only unravels the DNA around the damage, but also helps TFIIH in recognizing bulky lesions in DNA <ref>DOI 10.1093/nar/gkw102 </ref>. The DNA is then threaded through the central pore of XPD helicase, which then opens up the double helix. <br /> <br /> == Disease ==<br /> The NER pathway consists of 28 genes, three of which are part of TFIIH, and mutations in many of these are associated with a set of diseases that are similar but have marked differences <ref name="Kraemer">PMID: 17276014 </ref>. Mutations in XPD helicase are associated with three distinct diseases: [https://ghr.nlm.nih.gov/condition/cockayne-syndrome Cockayne Syndrome (CS)], [https://ghr.nlm.nih.gov/condition/xeroderma-pigmentosum Xeroderma Pigmentosum (XP)], and [https://ghr.nlm.nih.gov/condition/trichothiodystrophy trichothiodystrophy (TTD)] <ref>DOI 10.1093/nar/gkv472</ref>. The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation <ref name="Lifuss">PMID: 18510924 </ref>.<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity <ref name="Nance">PMID: 1308368 </ref>. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer. Some XP patients have neurological degeneration, which can be explained by the fact that neurons do not divide, and mutations that are not corrected by NER could accumulate and eventually lead to cell death <ref name="Kraemer">PMID: 17276014 </ref>. TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity <ref name="Hashimoto">PMID: 19808800 </ref>. It has been proposed that specific mutations in XPD helicase affect the transcription activities of TFIIH more than its repair activities, resulting in development issues that lead to intellectual disabilities <ref name="Kraemer">PMID: 17276014 </ref>. Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. Different types of mutations in XPD helicase as well as interactions between XPD helicase mutations and defects in other NER proteins can result in these different diseases. Due to the complexity of these interactions, little is known about the molecular basis for the differences in these diseases <ref name="Kraemer">PMID: 17276014 </ref>. <br /> <br /> == Structure ==<br /> XPD helicase's catalytic core is composed of four domains, HD1, HD2, 4FeS, and Arch domains. Residues 7-283 form the Helicase ATP binding domain(<scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene>), where ATP itself binds at residues 42-49, (<scene name='72/728075/Nucleotide_binding/4'>ATP Binding</scene>). Interaction with the gene MMS19 is mediated by region consisting of residues 438-637. Residues 234-237 form the motif which is the DEAH box of this transcription factor which is where the unwinding of DNA is performed (<scene name='72/728075/Deah_box/1'>DEAH Box</scene>). Iron Sulfur bonding residues consist of C116, C134, C155, and C160,(<scene name='72/728075/Iron_sulfur/2'>Iron Sulfur Binding</scene>). Features of Cockayne Syndrome and Xeroderma pigmentosum have been associated with the point mutation G602D, and the point mutation L461V is associated with [http://www.omim.org/entry/601675 TTD1] <ref>DOI 10.1093/nar/gku989 </ref>. <br /> <br /> == Structural highlights ==<br /> <br /> <scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene><br /> <br /> <scene name='72/728075/Nucleotide_binding/3'>ATP Binding</scene><br /> <br /> <scene name='72/728075/Deah_box/1'>DEAH Box</scene><br /> <br /> <scene name='72/728075/Iron_sulfur/1'>Iron Sulfur Binding</scene><br /> <br /> <scene name='72/728075/Arch_domain/1'>Arch Domain</scene><br /> <br /> <scene name='72/728075/Hd1/1'>HD1 Domain</scene><br /> <br /> <br /> <br /> <br /> == References ==<br /> <references/></div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2588566 XPD Helicase (3CRV) 2016-04-27T01:17:24Z

<p>Bashir Noor: </p> <hr /> <div><StructureSection load='3CRV' size='450' side='right' caption='XPD helicase, 3CRV'><br /> <br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) helicase is a subunit of [http://proteopedia.org/wiki/index.php/Category:Tfiih Transcription Factor IIH (TFIIH)], which aids in [http://proteopedia.org/wiki/index.php/Category:Transcription_initiation transcription initiation] and DNA repair. XPD helicse unwinds DNA, allowing other [http://proteopedia.org/wiki/index.php/Category:Dna-repair DNA repair enzymes] to access and correct damaged regions in the DNA. XPD helicase helps to fix DNA damaged by ultraviolet (UV) light radiation, therefore mutations in XPD helicase results in diseases characterized by light sensitivity. <br /> <br /> == Function ==<br /> XPD helicase is an essential subunit of the general transcription factor IIH (TFIIH), which is a complex that, along with other general transcription factors, helps to initiate transcription and repair damaged DNA <ref name="Mydikova">PMID: 20429618</ref>. XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme <ref name="Lifuss">PMID: 18510924 </ref>. Helicases are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes, like polymerases, can act upon the DNA <ref name="Tuteja">PMID: 15128295 </ref>. In the context of DNA repair, helicases unwind DNA and other enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to UV radiation, adjacent nucleotide bases, often thymines, can react and form bulky pyrimidine dimers, which can block enzymes that work on DNA <ref name="Vink">PMID: 11809365 </ref>. For example, during DNA replication, [http://proteopedia.org/wiki/index.php/Category:Thymine_Dimers thymine dimers] do not fit into the active site of DNA polymerases smoothly, sometimes resulting in mismatched nucleotides. To fix this type of damage on single strands of DNA, cells employ a process called [http://proteopedia.org/wiki/index.php/Category:Nucleotide_excision_repair nucleotide excision repair (NER)] <ref name="Lifuss">PMID: 18510924 </ref>. This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove the damaged DNA. <br /> <br /> Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP <ref name="Buechner">PMID: 24338567 </ref>. The ATP-dependent helicase activity of XPD helicase, however is only required for NER, even though TFIIH participates in both repair and transcription initiation <ref name="Kuper">PMID: 25268380 </ref>. XPD helicase not only unravels the DNA around the damage, but also helps TFIIH in recognizing bulky lesions in DNA <ref>DOI 10.1093/nar/gkw102 </ref>. The DNA is then threaded through the central pore of XPD helicase, which then opens up the double helix. <br /> <br /> == Disease ==<br /> The NER pathway consists of 28 genes, three of which are part of TFIIH, and mutations in many of these are associated with a set of diseases that are similar but have marked differences <ref name="Kraemer">PMID: 17276014 </ref>. Mutations in XPD helicase are associated with three distinct diseases: [https://ghr.nlm.nih.gov/condition/cockayne-syndrome Cockayne Syndrome (CS)], [https://ghr.nlm.nih.gov/condition/xeroderma-pigmentosum Xeroderma Pigmentosum (XP)], and [https://ghr.nlm.nih.gov/condition/trichothiodystrophy trichothiodystrophy (TTD)] <ref>DOI 10.1093/nar/gkv472</ref>. The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation <ref name="Lifuss">PMID: 18510924 </ref>.<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity <ref name="Nance">PMID: 1308368 </ref>. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer. Some XP patients have neurological degeneration, which can be explained by the fact that neurons do not divide, and mutations that are not corrected by NER could accumulate and eventually lead to cell death <ref name="Kraemer">PMID: 17276014 </ref>. TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity <ref name="Hashimoto">PMID: 19808800 </ref>. It has been proposed that specific mutations in XPD helicase affect the transcription activities of TFIIH more than its repair activities, resulting in development issues that lead to intellectual disabilities <ref name="Kraemer">PMID: 17276014 </ref>. Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. Different types of mutations in XPD helicase as well as interactions between XPD helicase mutations and defects in other NER proteins can result in these different diseases. Due to the complexity of these interactions, little is known about the molecular basis for the differences in these diseases <ref name="Kraemer">PMID: 17276014 </ref>. <br /> <br /> == Structure ==<br /> XPD helicase is made up of alpha helices and beta sheets and contains one main domain, a DNA interaction interface. There are two motifs, one of which performs the function of unwinding the DNA strand. The second motif, located at residues 682-695, directs XPD helicase to the nucleus, as it is the nuclear localization signal. Residues 7-283 form the Helicase ATP binding domain(<scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene>), where ATP itself binds at residues 42-49, (<scene name='72/728075/Nucleotide_binding/4'>ATP Binding</scene>). Interaction with the gene MMS19 is mediated by region consisting of residues 438-637. Residues 234-237 form the motif which is the DEAH box of this transcription factor which is where the unwinding of DNA is performed (<scene name='72/728075/Deah_box/1'>DEAH Box</scene>). Iron Sulfur bonding residues consist of C116, C134, C155, and C160,(<scene name='72/728075/Iron_sulfur/2'>Iron Sulfur Binding</scene>). Features of Cockayne Syndrome and Xeroderma pigmentosum have been associated with the point mutation G602D, and the point mutation L461V is associated with [http://www.omim.org/entry/601675 TTD1] <ref>DOI 10.1093/nar/gku989 </ref>. <br /> <br /> == Structural highlights ==<br /> <br /> <scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene><br /> <br /> <scene name='72/728075/Nucleotide_binding/3'>ATP Binding</scene><br /> <br /> <scene name='72/728075/Deah_box/1'>DEAH Box</scene><br /> <br /> <scene name='72/728075/Iron_sulfur/1'>Iron Sulfur Binding</scene><br /> <br /> <scene name='72/728075/Arch_domain/1'>Arch Domain</scene><br /> <br /> <br /> <br /> <br /> == References ==<br /> <references/></div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2588551 XPD Helicase (3CRV) 2016-04-27T00:55:07Z

<p>Bashir Noor: </p> <hr /> <div><StructureSection load='3CRV' size='450' side='right' caption='XPD helicase, 3CRV'><br /> <br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) helicase is a subunit of transcription factor IIH (TFIIH), which aids in transcription initiation and DNA repair. XPD helicse unwinds DNA, allowing other DNA repair enzymes to access and correct damaged regions in the DNA. XPD helicase helps to fix DNA damaged by ultraviolet (UV) light radiation, therefore mutations in XPD helicase results in diseases characterized by light sensitivity. <br /> <br /> == Function ==<br /> XPD helicase is an essential subunit of the general transcription factor IIH (TFIIH), which is a complex that, along with other general transcription factors, helps to initiate transcription and repair damaged DNA <ref name="Mydikova">PMID: 20429618</ref>. XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme <ref name="Lifuss">PMID: 18510924 </ref>. Helicases are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes, like polymerases, can act upon the DNA <ref name="Tuteja">PMID: 15128295 </ref>. In the context of DNA repair, helicases unwind DNA and other enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to UV radiation, adjacent nucleotide bases, often thymines, can react and form bulky pyrimidine dimers, which can block enzymes that work on DNA <ref name="Vink">PMID: 11809365 </ref>. For example, during DNA replication, thymine dimers do not fit into the active site of DNA polymerases smoothly, sometimes resulting in mismatched nucleotides. To fix this type of damage on single strands of DNA, cells employ a process called nucleotide excision repair (NER) <ref name="Lifuss">PMID: 18510924 </ref>. This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove the damaged DNA. <br /> <br /> Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP <ref name="Buechner">PMID: 24338567 </ref>. The ATP-dependent helicase activity of XPD helicase, however is only required for NER, even though TFIIH participates in both repair and transcription initiation <ref name="Kuper">PMID: 25268380 </ref>. XPD helicase not only unravels the DNA around the damage, but also helps TFIIH in recognizing bulky lesions in DNA <ref>DOI 10.1093/nar/gkw102 </ref>. The DNA is then threaded through the central pore of XPD helicase, which then opens up the double helix. <br /> <br /> == Disease ==<br /> The NER pathway consists of 28 genes, three of which are part of TFIIH, and mutations in many of these are associated with a set of diseases that are similar but have marked differences <ref name="Kraemer">PMID: 17276014 </ref>. Mutations in XPD helicase are associated with three distinct diseases: Cockayne Syndrome (CS), Xeroderma Pigmentosum (XP), and trichothiodystrophy (TTD) <ref>DOI 10.1093/nar/gkv472</ref>. The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation <ref name="Lifuss">PMID: 18510924 </ref>.<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity <ref name="Nance">PMID: 1308368 </ref>. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer. Some XP patients have neurological degeneration, which can be explained by the fact that neurons do not divide, and mutations that are not corrected by NER could accumulate and eventually lead to cell death <ref name="Kraemer">PMID: 17276014 </ref>. TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity <ref name="Hashimoto">PMID: 19808800 </ref>. It has been proposed that specific mutations in XPD helicase affect the transcription activities of TFIIH more than its repair activities, resulting in development issues that lead to intellectual disabilities <ref name="Kraemer">PMID: 17276014 </ref>. Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. Different types of mutations in XPD helicase as well as interactions between XPD helicase mutations and defects in other NER proteins can result in these different diseases. Due to the complexity of these interactions, little is known about the molecular basis for the differences in these diseases <ref name="Kraemer">PMID: 17276014 </ref>. <br /> <br /> == Structure ==<br /> XPD helicase is made up of alpha helices and beta sheets and contains one main domain, a DNA interaction interface. There are two motifs, one of which performs the function of unwinding the DNA strand. The second motif, located at residues 682-695, directs XPD helicase to the nucleus, as it is the nuclear localization signal. Residues 7-283 form the Helicase ATP binding domain(<scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene>), where ATP itself binds at residues 42-49, (<scene name='72/728075/Nucleotide_binding/4'>ATP Binding</scene>). Interaction with the gene MMS19 is mediated by region consisting of residues 438-637. Residues 234-237 form the motif which is the DEAH box of this transcription factor which is where the unwinding of DNA is performed (<scene name='72/728075/Deah_box/1'>DEAH Box</scene>). Iron Sulfur bonding residues consist of C116, C134, C155, and C160,(<scene name='72/728075/Iron_sulfur/2'>Iron Sulfur Binding</scene>). Features of Cockayne Syndrome and Xeroderma pigmentosum have been associated with the point mutation G602D, and the point mutation L461V is associated with TTD1 <ref>DOI 10.1093/nar/gku989 </ref>. <br /> <br /> == Structural highlights ==<br /> <br /> <scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene><br /> <br /> <scene name='72/728075/Nucleotide_binding/3'>ATP Binding</scene><br /> <br /> <scene name='72/728075/Deah_box/1'>DEAH Box</scene><br /> <br /> <scene name='72/728075/Iron_sulfur/1'>Iron Sulfur Binding</scene><br /> <br /> <scene name='72/728075/Cysteine_iron_binding/3'>TextToBeDisplayed</scene><br /> <br /> <br /> <br /> <br /> == References ==<br /> <references/></div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2588548 XPD Helicase (3CRV) 2016-04-27T00:53:58Z

<p>Bashir Noor: </p> <hr /> <div><StructureSection load='3CRV' size='450' side='right' caption='XPD helicase, 3CRV'><br /> <br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) helicase is a subunit of transcription factor IIH (TFIIH), which aids in transcription initiation and DNA repair. XPD helicse unwinds DNA, allowing other DNA repair enzymes to access and correct damaged regions in the DNA. XPD helicase helps to fix DNA damaged by ultraviolet (UV) light radiation, therefore mutations in XPD helicase results in diseases characterized by light sensitivity. <br /> <br /> == Function ==<br /> XPD helicase is an essential subunit of the general transcription factor IIH (TFIIH), which is a complex that, along with other general transcription factors, helps to initiate transcription and repair damaged DNA <ref name="Mydikova">PMID: 20429618</ref>. XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme <ref name="Lifuss">PMID: 18510924 </ref>. Helicases are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes, like polymerases, can act upon the DNA <ref name="Tuteja">PMID: 15128295 </ref>. In the context of DNA repair, helicases unwind DNA and other enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to UV radiation, adjacent nucleotide bases, often thymines, can react and form bulky pyrimidine dimers, which can block enzymes that work on DNA <ref name="Vink">PMID: 11809365 </ref>. For example, during DNA replication, thymine dimers do not fit into the active site of DNA polymerases smoothly, sometimes resulting in mismatched nucleotides. To fix this type of damage on single strands of DNA, cells employ a process called nucleotide excision repair (NER) <ref name="Lifuss">PMID: 18510924 </ref>. This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove the damaged DNA. <br /> <br /> Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP <ref name="Buechner">PMID: 24338567 </ref>. The ATP-dependent helicase activity of XPD helicase, however is only required for NER, even though TFIIH participates in both repair and transcription initiation <ref name="Kuper">PMID: 25268380 </ref>. XPD helicase not only unravels the DNA around the damage, but also helps TFIIH in recognizing bulky lesions in DNA <ref>DOI 10.1093/nar/gkw102 </ref>. The DNA is then threaded through the central pore of XPD helicase, which then opens up the double helix. <br /> <br /> == Disease ==<br /> The NER pathway consists of 28 genes, three of which are part of TFIIH, and mutations in many of these are associated with a set of diseases that are similar but have marked differences <ref name="Kraemer">PMID: 17276014 </ref>. Mutations in XPD helicase are associated with three distinct diseases: Cockayne Syndrome (CS), Xeroderma Pigmentosum (XP), and trichothiodystrophy (TTD) <ref>DOI 10.1093/nar/gkv472</ref>. The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation <ref name="Lifuss">PMID: 18510924 </ref>.<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity <ref name="Nance">PMID: 1308368 </ref>. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer. Some XP patients have neurological degeneration, which can be explained by the fact that neurons do not divide, and mutations that are not corrected by NER could accumulate and eventually lead to cell death <ref name="Kraemer">PMID: 17276014 </ref>. TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity <ref name="Hashimoto">PMID: 19808800 </ref>. It has been proposed that specific mutations in XPD helicase affect the transcription activities of TFIIH more than its repair activities, resulting in development issues that lead to intellectual disabilities <ref name="Kraemer">PMID: 17276014 </ref>. Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. Different types of mutations in XPD helicase as well as interactions between XPD helicase mutations and defects in other NER proteins can result in these different diseases. Due to the complexity of these interactions, little is known about the molecular basis for the differences in these diseases <ref name="Kraemer">PMID: 17276014 </ref>. <br /> <br /> == Structure ==<br /> XPD helicase is made up of alpha helices and beta sheets and contains one main domain, a DNA interaction interface. There are two motifs, one of which performs the function of unwinding the DNA strand. The second motif, located at residues 682-695, directs XPD helicase to the nucleus, as it is the nuclear localization signal. Residues 7-283 form the Helicase ATP binding domain(<scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene>), where ATP itself binds at residues 42-49, (<scene name='72/728075/Nucleotide_binding/4'>ATP Binding</scene>). Interaction with the gene MMS19 is mediated by region consisting of residues 438-637. Residues 234-237 form the motif which is the DEAH box of this transcription factor which is where the unwinding of DNA is performed (<scene name='72/728075/Deah_box/1'>DEAH Box</scene>). Iron Sulfur bonding residues consist of C116, C134, C155, and C160,(<scene name='72/728075/Iron_sulfur/2'>TextToBeDisplayed</scene>). Features of Cockayne Syndrome and Xeroderma pigmentosum have been associated with the point mutation G602D, and the point mutation L461V is associated with TTD1 <ref>DOI 10.1093/nar/gku989 </ref>. <br /> <br /> == Structural highlights ==<br /> <br /> <scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene><br /> <br /> <scene name='72/728075/Nucleotide_binding/3'>ATP Binding</scene><br /> <br /> <scene name='72/728075/Deah_box/1'>DEAH Box</scene><br /> <br /> <scene name='72/728075/Iron_sulfur/1'>Iron Sulfur Binding</scene><br /> <br /> <scene name='72/728075/Cysteine_iron_binding/3'>TextToBeDisplayed</scene><br /> <br /> <br /> <br /> <br /> == References ==<br /> <references/></div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2588540 XPD Helicase (3CRV) 2016-04-27T00:32:32Z

<p>Bashir Noor: </p> <hr /> <div><StructureSection load='3CRV' size='450' side='right' caption='XPD helicase, 3CRV'><br /> <br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) helicase is a subunit of transcription factor IIH (TFIIH), which aids in transcription initiation and DNA repair. XPD helicse unwinds DNA, allowing other DNA repair enzymes to access and correct damaged regions in the DNA. XPD helicase helps to fix DNA damaged by ultraviolet (UV) light radiation, therefore mutations in XPD helicase results in diseases characterized by light sensitivity. <br /> <br /> == Function ==<br /> XPD helicase is an essential subunit, of the general transcription factor IIH (TFIIH), which is a complex that, along with other general transcription factors, helps to initiate transcription and repair damaged DNA <ref name="Mydikova">PMID: 20429618</ref>. XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme <ref name="Lifuss">PMID: 18510924 </ref>. Helicases, of which XPD helicase is an example, are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes, like polymerases, can act upon the DNA <ref name="Tuteja">PMID: 15128295 </ref>. In the context of DNA repair, helicases unwind DNA, and other enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to ultraviolet (UV) radiation, adjacent nucleotide bases, often thymines, can react and form bulky pyrimidine dimers, which can block enzymes that work on DNA <ref name="Vink">PMID: 11809365 </ref>. For example, during DNA replication, thymine dimers do not fit into the active site of DNA polymerases smoothly, sometimes resulting in mismatched nucleotides. To fix this type of damage on single strands of DNA, cells employ a process called nucleotide excision repair (NER) <ref name="Lifuss">PMID: 18510924 </ref>. This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove the damaged DNA. <br /> <br /> Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP <ref name="Buechner">PMID: 24338567 </ref>. The ATP-dependent helicase activity of XPD helicase, however, is only required for NER, even though TFIIH participates in both repair and transcription initiation <ref name="Kuper">PMID: 25268380 </ref>. XPD helicase not only unravels the DNA around the damage but also helps TFIIH in recognizing bulky lesions in DNA <ref>DOI 10.1093/nar/gkw102 </ref>. The DNA is then threaded through the central pore of XPD helicase, which then opens up the double helix. <br /> <br /> == Disease ==<br /> The NER pathway consists of 28 genes, three of which are part of TFIIH, and mutations in many of these are associated with a set of diseases that are similar but have marked differences <ref name="Kraemer">PMID: 17276014 </ref>. Mutations in XPD helicase are associated with three distinct diseases: Cockayne Syndrome (CS), Xeroderma Pigmentosum (XP), and trichothiodystrophy (TTD) <ref>DOI 10.1093/nar/gkv472</ref>. The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation <ref name="Lifuss">PMID: 18510924 </ref>.<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity <ref name="Nance">PMID: 1308368 </ref>. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer. Some XP patients have neurological degeneration, which can be explained by the fact that neurons do not divide, and mutations that are not corrected by NER could accumulate and eventually lead to cell death <ref name="Kraemer">PMID: 17276014 </ref>. TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity <ref name="Hashimoto">PMID: 19808800 </ref>. It has been proposed that specific mutations in XPD helicase affect the transcription activities of TFIIH more than its repair activities, resulting in development issues that lead to intellectual disabilities <ref name="Kraemer">PMID: 17276014 </ref>. Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. Different types of mutations in XPD helicase as well as interactions between XPD helicase mutations and defects in other NER proteins can result in these different diseases. Due to the complexity of these interactions, little is known about the molecular basis for the differences in these diseases <ref name="Kraemer">PMID: 17276014 </ref>. <br /> <br /> == Structure ==<br /> The structure of the subunit XPD helicase contains one main domain, a DNA interaction interface, and two motifs, one of which performs the function of unwinding the DNA strand. Residues 7-283 form the Helicase ATP binding domain(<scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene>), where ATP itself binds at residues 42-49, (<scene name='72/728075/Nucleotide_binding/4'>ATP Binding</scene>). Interaction with the gene MMS19 is mediated by region consisting of residues 438-637. Residues 234-237 form the motif which is the DEAH box of this transcription factor which is where the unwinding of DNA is performed (<scene name='72/728075/Deah_box/1'>DEAH Box</scene>). A second motif located at residues 682-695 is where the nuclear localization signal is located. Iron Sulfur bonding residues consist of C116, C134, C155, and C160,(<scene name='72/728075/Iron_sulfur/1'>Iron Sulfur Binding</scene>). Features of Cockayne Syndrome and Xeroderma pigmentosum have been associated with point mutation G602D, and point mutation L461V is associated with TTD1 <ref>DOI 10.1093/nar/gku989 </ref>. <br /> <br /> == Structural highlights ==<br /> <scene name='72/728075/Alpha_helices/4'>Alpha Helices</scene><br /> <br /> <scene name='72/728075/Beta_sheet/3'>Beta Sheets</scene><br /> <br /> <scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene><br /> <br /> <scene name='72/728075/Nucleotide_binding/3'>ATP Binding</scene><br /> <br /> <scene name='72/728075/Deah_box/1'>DEAH Box</scene><br /> <br /> <scene name='72/728075/Iron_sulfur/1'>Iron Sulfur Binding</scene><br /> <br /> <scene name='72/728075/Cysteine_iron_binding/3'>TextToBeDisplayed</scene><br /> <br /> <br /> <br /> <br /> == References ==<br /> <references/></div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2588533 XPD Helicase (3CRV) 2016-04-27T00:07:32Z

<p>Bashir Noor: </p> <hr /> <div><StructureSection load='3CRV' size='450' side='right' caption='XPD helicase, 3CRV'><br /> <br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) helicase is a subunit of transcription factor IIH (TFIIH), which aids in transcription initiation and DNA repair. XPD helicse unwinds DNA, allowing other DNA repair enzymes to access and correct damaged regions in the DNA. Because the type of DNA damage that XPD helicase helps to fix is caused by UV light radiation, mutations in XPD helicase results in diseases characterized by light sensitivity. <br /> <br /> == Function ==<br /> XPD helicase is an essential subunit, of the general transcription factor IIH (TFIIH), which is a complex that, along with other general transcription factors, helps to initiate transcription and repair damaged DNA <ref name="Mydikova">PMID: 20429618</ref>. XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme <ref name="Lifuss">PMID: 18510924 </ref>. Helicases, of which XPD helicase is an example, are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes, like polymerases, can act upon the DNA <ref name="Tuteja">PMID: 15128295 </ref>. In the context of DNA repair, helicases unwind DNA, and other enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to ultraviolet (UV) radiation, adjacent nucleotide bases, often thymines, can react and form bulky pyrimidine dimers, which can block enzymes that work on DNA <ref name="Vink">PMID: 11809365 </ref>. For example, during DNA replication, thymine dimers do not fit into the active site of DNA polymerases smoothly, sometimes resulting in mismatched nucleotides. To fix this type of damage on single strands of DNA, cells employ a process called nucleotide excision repair (NER) <ref name="Lifuss">PMID: 18510924 </ref>. This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove the damaged DNA. <br /> <br /> Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP <ref name="Buechner">PMID: 24338567 </ref>. The ATP-dependent helicase activity of XPD helicase, however, is only required for NER, even though TFIIH participates in both repair and transcription initiation <ref name="Kuper">PMID: 25268380 </ref>. XPD helicase not only unravels the DNA around the damage but also helps TFIIH in recognizing bulky lesions in DNA <ref>DOI 10.1093/nar/gkw102 </ref>. The DNA is then threaded through the central pore of XPD helicase, which then opens up the double helix. <br /> <br /> == Disease ==<br /> The NER pathway consists of 28 genes, three of which are part of TFIIH, and mutations in many of these are associated with a set of diseases that are similar but marked differences <ref name="Kraemer">PMID: 17276014 </ref>. Mutations in XPD helicase are associated with three distinct diseases: Cockayne Syndrome (CS), Xeroderma Pigmentosum (XP), and trichothiodystrophy (TTD) <ref>DOI 10.1093/nar/gkv472</ref>. The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation <ref name="Lifuss">PMID: 18510924 </ref>.<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity <ref name="Nance">PMID: 1308368 </ref>. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer. Some XP patients have neurological degeneration. This is possibly due to the fact that neurons do not divide, and mutations that are not corrected by NER accumulate and eventually lead to cell death <ref name="Kraemer">PMID: 17276014 </ref>. TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity <ref name="Hashimoto">PMID: 19808800 </ref>. It has been proposed that specific mutations in XPD helicase affect the transcription activities of TFIIH more than its repair activities, resulting in development issues that lead to intellectual disabilities <ref name="Kraemer">PMID: 17276014 </ref>. Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. Different types of mutations in XPD helicase as well as interactions between XPD helicase defects and defects in other NER proteins can result in these different diseases. Due to the complexity of these interactions, little is known about the molecular basis for the differences in these diseases <ref name="Kraemer">PMID: 17276014 </ref>. <br /> <br /> == Structure ==<br /> The structure of the subunit XPD helicase contains one main domain, a DNA interaction interface, and two motifs, one of which performs the function of unwinding the DNA strand. Residues 7-283 form the Helicase ATP binding domain(<scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene>), where ATP itself binds at residues 42-49, (<scene name='72/728075/Nucleotide_binding/4'>ATP Binding</scene>). Interaction with the gene MMS19 is mediated by region consisting of residues 438-637. Residues 234-237 form the motif which is the DEAH box of this transcription factor which is where the unwinding of DNA is performed (<scene name='72/728075/Deah_box/1'>DEAH Box</scene>). A second motif located at residues 682-695 is where the nuclear localization signal is located. Iron Sulfur bonding residues consist of C116, C134, C155, and C160,(<scene name='72/728075/Iron_sulfur/1'>Iron Sulfur Binding</scene>). Features of Cockayne Syndrome and Xeroderma pigmentosum have been associated with point mutation G602D, and point mutation L461V is associated with TTD1 <ref>DOI 10.1093/nar/gku989 </ref>. <br /> <br /> == Structural highlights ==<br /> <scene name='72/728075/Alpha_helices/4'>Alpha Helices</scene><br /> <br /> <scene name='72/728075/Beta_sheet/3'>Beta Sheets</scene><br /> <br /> <scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene><br /> <br /> <scene name='72/728075/Nucleotide_binding/3'>ATP Binding</scene><br /> <br /> <scene name='72/728075/Deah_box/1'>DEAH Box</scene><br /> <br /> <scene name='72/728075/Iron_sulfur/1'>Iron Sulfur Binding</scene><br /> <br /> <br /> <br /> <br /> == References ==<br /> <references/></div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2588531 XPD Helicase (3CRV) 2016-04-26T23:47:38Z

<p>Bashir Noor: </p> <hr /> <div><StructureSection load='3CRV' size='450' side='right' caption='XPD helicase, 3CRV'><br /> <br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) helicase is a subunit of Transcription Factor IIH (TFIIH), which aids in transcription initiation and DNA repair. XPD helicse unwinds DNA, allowing other DNA repair enzymes to access and correct damaged regions in the DNA. Because the type of DNA damage that XPD helicase helps to fix is caused by UV light radiation, mutations in XPD helicase results in diseases characterized by light sensitivity. <br /> <br /> == Function ==<br /> XPD helicase is an essential subunit, of the general transcription factor IIH (TFIIH), which is a complex that, along with other general transcription factors, helps to initiate transcription and repair damaged DNA <ref name="Mydikova">PMID: 20429618</ref>. XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme <ref name="Lifuss">PMID: 18510924 </ref>. Helicases, of which XPD helicase is an example, are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes, like polymerases, can act upon the DNA <ref name="Tuteja">PMID: 15128295 </ref>. In the context of DNA repair, helicases unwind DNA, and other enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to ultraviolet (UV) radiation, adjacent nucleotide bases, often thymines, can react and form bulky pyrimidine dimers, which can block enzymes that work on DNA <ref name="Vink">PMID: 11809365 </ref>. For example, during DNA replication, thymine dimers do not fit into the active site of DNA polymerases smoothly, sometimes resulting in mismatched nucleotides. To fix this type of damage on single strands of DNA, cells employ a process called nucleotide excision repair (NER) <ref name="Lifuss">PMID: 18510924 </ref>. This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove the damaged DNA. <br /> <br /> Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP <ref name="Buechner">PMID: 24338567 </ref>. The ATP-dependent helicase activity of XPD helicase, however, is only required for NER, even though TFIIH participates in both repair and transcription initiation <ref name="Kuper">PMID: 25268380 </ref>. XPD helicase not only unravels the DNA around the damage but also helps TFIIH in recognizing bulky lesions in DNA <ref>DOI 10.1093/nar/gkw102 </ref>. The DNA is then threaded through the central pore of XPD helicase, which then opens up the double helix. <br /> <br /> == Disease ==<br /> The NER pathway consists of 28 genes, three of which are part of TFIIH, and mutations in many of these are associated with a set of diseases that are similar but marked differences <ref name="Kraemer">PMID: 17276014 </ref>. Mutations in XPD helicase are associated with three distinct diseases: Cockayne Syndrome (CS), Xeroderma Pigmentosum (XP), and trichothiodystrophy (TTD) <ref>DOI 10.1093/nar/gkv472</ref>. The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation <ref name="Lifuss">PMID: 18510924 </ref>.<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity <ref name="Nance">PMID: 1308368 </ref>. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer. Some XP patients have neurological degeneration. This is possibly due to the fact that neurons do not divide, and mutations that are not corrected by NER accumulate and eventually lead to cell death <ref name="Kraemer">PMID: 17276014 </ref>. TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity <ref name="Hashimoto">PMID: 19808800 </ref>. It has been proposed that specific mutations in XPD helicase affect the transcription activities of TFIIH more than its repair activities, resulting in development issues that lead to intellectual disabilities <ref name="Kraemer">PMID: 17276014 </ref>. Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. Different types of mutations in XPD helicase as well as interactions between XPD helicase defects and defects in other NER proteins can result in these different diseases. Due to the complexity of these interactions, little is known about the molecular basis for the differences in these diseases <ref name="Kraemer">PMID: 17276014 </ref>. <br /> <br /> == Structure ==<br /> The structure of the subunit XPD helicase contains one main domain, a DNA interaction interface, and two motifs, one of which performs the function of unwinding the DNA strand. Residues 7-283 form the Helicase ATP binding domain(<scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene>), where ATP itself binds at residues 42-49, (<scene name='72/728075/Nucleotide_binding/3'>ATP Binding</scene>). Interaction with the gene MMS19 is mediated by region consisting of residues 438-637. Residues 234-237 form the motif which is the DEAH box of this transcription factor which is where the unwinding of DNA is performed (<scene name='72/728075/Deah_box/1'>DEAH Box</scene>). A second motif located at residues 682-695 is where the nuclear localization signal is located. Iron Sulfur bonding residues consist of C116, C134, C155, and C160,(<scene name='72/728075/Iron_sulfur/1'>Iron Sulfur Binding</scene>). Features of Cockayne Syndrome and Xeroderma pigmentosum have been associated with point mutation G602D, and point mutation L461V is associated with TTD1 <ref>DOI 10.1093/nar/gku989 </ref>. <br /> <br /> == Structural highlights ==<br /> <scene name='72/728075/Alpha_helices/4'>Alpha Helices</scene><br /> <br /> <scene name='72/728075/Beta_sheet/3'>Beta Sheets</scene><br /> <br /> <scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene><br /> <br /> <scene name='72/728075/Nucleotide_binding/3'>ATP Binding</scene><br /> <br /> <scene name='72/728075/Deah_box/1'>DEAH Box</scene><br /> <br /> <scene name='72/728075/Iron_sulfur/1'>Iron Sulfur Binding</scene><br /> <br /> <br /> <br /> <br /> == References ==<br /> <references/></div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2588530 XPD Helicase (3CRV) 2016-04-26T23:44:21Z

<p>Bashir Noor: </p> <hr /> <div><StructureSection load='3CRV' size='450' side='right' caption='XPD helicase, 3CRV'><br /> <br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) helicase is a subunit of Transcription Factor IIH (TFIIH), which aids in transcription initiation and DNA repair. XPD helicse unwinds DNA, allowing other DNA repair enzymes to access and correct damaged regions in the DNA. Because the type of DNA damage that XPD helicase helps to fix is caused by UV light radiation, mutations in XPD helicase results in diseases characterized by light sensitivity. <br /> <br /> == Function ==<br /> XPD helicase is an essential subunit, of the general transcription factor IIH (TFIIH), which is a complex that, along with other general transcription factors, helps to initiate transcription and repair damaged DNA <ref name="Mydikova">PMID: 20429618</ref>. XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme <ref name="Lifuss">PMID: 18510924 </ref>. Helicases, of which XPD helicase is an example, are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes, like polymerases, can act upon the DNA <ref name="Tuteja">PMID: 15128295 </ref>. In the context of DNA repair, helicases unwind DNA, and other enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to ultraviolet (UV) radiation, adjacent nucleotide bases, often thymines, can react and form bulky pyrimidine dimers, which can block enzymes that work on DNA <ref name="Vink">PMID: 11809365 </ref>. For example, during DNA replication, thymine dimers do not fit into the active site of DNA polymerases smoothly, sometimes resulting in mismatched nucleotides. To fix this type of damage on single strands of DNA, cells employ a process called nucleotide excision repair (NER) <ref name="Lifuss">PMID: 18510924 </ref>. This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove the damaged DNA. <br /> <br /> Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP <ref name="Buechner">PMID: 24338567 </ref>. The ATP-dependent helicase activity of XPD helicase, however, is only required for NER, even though TFIIH participates in both repair and transcription initiation <ref name="Kuper">PMID: 25268380 </ref>. XPD helicase not only unravels the DNA around the damage but also helps TFIIH in recognizing bulky lesions in DNA <ref>DOI 10.1093/nar/gkw102 </ref>. The DNA is then threaded through the central pore of XPD helicase, which then opens up the double helix. <br /> <br /> == Disease ==<br /> The NER pathway consists of 28 genes, three of which are part of TFIIH, and mutations in many of these are associated with a set of diseases that are similar but marked differences <ref name="Kraemer">PMID: 17276014 </ref>. Mutations in XPD helicase are associated with three distinct diseases: Cockayne Syndrome (CS), Xeroderma Pigmentosum (XP), and trichothiodystrophy (TTD) <ref>DOI 10.1093/nar/gkv472</ref>. The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation <ref name="Lifuss">PMID: 18510924 </ref>.<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity <ref name="Nance">PMID: 1308368 </ref>. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer. Some XP patients have neurological degeneration. This is possibly due to the fact that neurons do not divide, and mutations that are not corrected by NER accumulate and eventually lead to cell death <ref name="Kraemer">PMID: 17276014 </ref>. TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity <ref name="Hashimoto">PMID: 19808800 </ref>. It has been proposed that specific mutations in XPD helicase affect the transcription activities of TFIIH more than its repair activities, resulting in development issues that lead to intellectual disabilities <ref name="Kraemer">PMID: 17276014 </ref>. Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. Different types of mutations in XPD helicase as well as interactions between XPD helicase defects and defects in other NER proteins can result in these different diseases. Due to the complexity of these interactions, little is known about the molecular basis for the differences in these diseases <ref name="Kraemer">PMID: 17276014 </ref>. <br /> <br /> == Structure Description ==<br /> The structure of the subunit XPD helicase contains one main domain, a DNA interaction interface, and two motifs, one of which performs the function of unwinding the DNA strand. Residues 7-283 form the Helicase ATP binding domain(<scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene>), where ATP itself binds at residues 42-49, (<scene name='72/728075/Nucleotide_binding/3'>ATP Binding</scene>). Interaction with the gene MMS19 is mediated by region consisting of residues 438-637. Residues 234-237 form the motif which is the DEAH box of this transcription factor which is where the unwinding of DNA is performed (<scene name='72/728075/Deah_box/1'>DEAH Box</scene>). A second motif located at residues 682-695 is where the nuclear localization signal is located. Iron Sulfur bonding residues consist of C116, C134, C155, and C160,(<scene name='72/728075/Iron_sulfur/1'>Iron Sulfur Binding</scene>). Features of Cockayne Syndrome and Xeroderma pigmentosum have been associated with point mutation G602D, and point mutation L461V is associated with TTD1 <ref>DOI 10.1093/nar/gku989 </ref>. <br /> <br /> == Structural highlights ==<br /> <scene name='72/728075/Alpha_helices/4'>Alpha Helices</scene><br /> <br /> <scene name='72/728075/Beta_sheet/3'>Beta Sheets</scene><br /> <br /> <scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene><br /> <br /> <scene name='72/728075/Nucleotide_binding/3'>ATP Binding</scene><br /> <br /> <scene name='72/728075/Deah_box/1'>DEAH Box</scene><br /> <br /> <scene name='72/728075/Iron_sulfur/1'>Iron Sulfur Binding</scene><br /> <br /> <br /> <br /> <br /> == References ==<br /> <references/></div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2588368 XPD Helicase (3CRV) 2016-04-25T18:13:20Z

<p>Bashir Noor: </p> <hr /> <div><StructureSection load='3CRV' size='450' side='right' scene='Journal:BMC:3/Cv/1' caption='XPD helicase, 3CRV'><br /> <br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) helicase is a subunit of Transcription Factor IIH (TFIIH), which aids in transcription initiation and DNA repair. XPD helicse unwinds DNA, allowing other DNA repair enzymes to access and correct damaged regions in the DNA. Because the type of DNA damage that XPD helicase helps to fix is caused by UV light radiation, mutations in XPD helicase results in diseases characterized by light sensitivity. <br /> <br /> == Function ==<br /> XPD helicase is an essential subunit, of the general transcription factor IIH (TFIIH), which is a complex that, along with other general transcription factors, helps to initiate transcription and repair damaged DNA <ref name="Mydikova">PMID: 20429618</ref>. XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme <ref name="Lifuss">PMID: 18510924 </ref>. Helicases, of which XPD helicase is an example, are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes, like polymerases, can act upon the DNA <ref name="Tuteja">PMID: 15128295 </ref>. In the context of DNA repair, helicases unwind DNA, and other enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to ultraviolet (UV) radiation, adjacent nucleotide bases, often thymines, can react and form bulky pyrimidine dimers, which can block enzymes that work on DNA <ref name="Vink">PMID: 11809365 </ref>. For example, during DNA replication, thymine dimers do not fit into the active site of DNA polymerases smoothly, sometimes resulting in mismatched nucleotides. To fix this type of damage on single strands of DNA, cells employ a process called nucleotide excision repair (NER) <ref name="Lifuss">PMID: 18510924 </ref>. This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove the damaged DNA. <br /> <br /> Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP <ref name="Buechner">PMID: 24338567 </ref>. The ATP-dependent helicase activity of XPD helicase, however, is only required for NER, even though TFIIH participates in both repair and transcription initiation <ref name="Kuper">PMID: 25268380 </ref>. XPD helicase not only unravels the DNA around the damage but also helps TFIIH in recognizing bulky lesions in DNA <ref>DOI 10.1093/nar/gkw102 </ref>. The DNA is then threaded through the central pore of XPD helicase, which then opens up the double helix. <br /> <br /> == Disease ==<br /> The NER pathway consists of 28 genes, three of which are part of TFIIH, and mutations in many of these are associated with a set of diseases that are similar but marked differences <ref name="Kraemer">PMID: 17276014 </ref>. Mutations in XPD helicase are associated with three distinct diseases: Cockayne Syndrome (CS), Xeroderma Pigmentosum (XP), and trichothiodystrophy (TTD) <ref>DOI 10.1093/nar/gkv472</ref>. The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation <ref name="Lifuss">PMID: 18510924 </ref>.<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity <ref name="Nance">PMID: 1308368 </ref>. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer. Some XP patients have neurological degeneration. This is possibly due to the fact that neurons do not divide, and mutations that are not corrected by NER accumulate and eventually lead to cell death <ref name="Kraemer">PMID: 17276014 </ref>. TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity <ref name="Hashimoto">PMID: 19808800 </ref>. It has been proposed that specific mutations in XPD helicase affect the transcription activities of TFIIH more than its repair activities, resulting in development issues that lead to intellectual disabilities <ref name="Kraemer">PMID: 17276014 </ref>. Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. Different types of mutations in XPD helicase as well as interactions between XPD helicase defects and defects in other NER proteins can result in these different diseases. Due to the complexity of these interactions, little is known about the molecular basis for the differences in these diseases <ref name="Kraemer">PMID: 17276014 </ref>. <br /> <br /> == Structure Description ==<br /> The structure of the subunit XPD helicase contains one main domain, a DNA interaction interface, and two motifs, one of which performs the function of unwinding the DNA strand. Residues 7-283 form the Helicase ATP binding domain(<scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene>), where ATP itself binds at residues 42-49, (<scene name='72/728075/Nucleotide_binding/3'>ATP Binding</scene>). Interaction with the gene MMS19 is mediated by region consisting of residues 438-637. Residues 234-237 form the motif which is the DEAH box of this transcription factor which is where the unwinding of DNA is performed (<scene name='72/728075/Deah_box/1'>DEAH Box</scene>). A second motif located at residues 682-695 is where the nuclear localization signal is located. Iron Sulfur bonding residues consist of C116, C134, C155, and C160,(<scene name='72/728075/Iron_sulfur/1'>Iron Sulfur Binding</scene>). Features of Cockayne Syndrome and Xeroderma pigmentosum have been associated with point mutation G602D, and point mutation L461V is associated with TTD1 <ref>DOI 10.1093/nar/gku989 </ref>. <br /> <br /> == Structural highlights ==<br /> <scene name='72/728075/Alpha_helices/4'>Alpha Helices</scene><br /> <br /> <scene name='72/728075/Beta_sheet/3'>Beta Sheets</scene><br /> <br /> <scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene><br /> <br /> <scene name='72/728075/Nucleotide_binding/3'>ATP Binding</scene><br /> <br /> <scene name='72/728075/Deah_box/1'>DEAH Box</scene><br /> <br /> <scene name='72/728075/Iron_sulfur/1'>Iron Sulfur Binding</scene><br /> <br /> <br /> <br /> <br /> == References ==<br /> <references/></div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2588367 XPD Helicase (3CRV) 2016-04-25T18:08:11Z

<p>Bashir Noor: </p> <hr /> <div><StructureSection load='3CRV' size='450' side='right' scene='Journal:BMC:3/Cv/1' caption='XPD helicase, 3CRV'><br /> <br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) helicase is a subunit of Transcription Factor IIH (TFIIH), which aids in transcription initiation and DNA repair. XPD helicse unwinds DNA, allowing other DNA repair enzymes to access and correct damaged regions in the DNA. Because the type of DNA damage that XPD helicase helps to fix is caused by UV light radiation, mutations in XPD helicase results in diseases characterized by light sensitivity. <br /> <br /> == Function ==<br /> XPD helicase is an essential subunit, of the general transcription factor IIH (TFIIH), which is a complex that, along with other general transcription factors, helps to initiate transcription and repair damaged DNA <ref name="Mydikova">PMID: 20429618</ref>. XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme <ref name="Lifuss">PMID: 18510924 </ref>. Helicases, of which XPD helicase is an example, are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes, like polymerases, can act upon the DNA <ref name="Tuteja">PMID: 15128295 </ref>. In the context of DNA repair, helicases unwind DNA, and other enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to ultraviolet (UV) radiation, adjacent nucleotide bases, often thymines, can react and form bulky pyrimidine dimers, which can block enzymes that work on DNA <ref name="Vink">PMID: 11809365 </ref>. For example, during DNA replication, thymine dimers do not fit into the active site of DNA polymerases smoothly, sometimes resulting in mismatched nucleotides. To fix this type of damage on single strands of DNA, cells employ a process called nucleotide excision repair (NER) <ref name="Lifuss">PMID: 18510924 </ref>. This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove the damaged DNA. <br /> <br /> Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP <ref name="Buechner">PMID: 24338567 </ref>. The ATP-dependent helicase activity of XPD helicase, however, is only required for NER, even though TFIIH participates in both repair and transcription initiation <ref name="Kuper">PMID: 25268380 </ref>. XPD helicase not only unravels the DNA around the damage but also helps TFIIH in recognizing bulky lesions in DNA <ref>DOI 10.1093/nar/gkw102 </ref>. The DNA is then threaded through the central pore of XPD helicase, which then opens up the double helix. <br /> <br /> == Disease ==<br /> The NER pathway consists of 28 genes, three of which are part of TFIIH, and mutations in many of these are associated with a set of diseases that are similar but marked differences <ref name="Kraemer">PMID: 17276014 </ref>. Mutations in XPD helicase are associated with three distinct diseases: Cockayne Syndrome (CS), Xeroderma Pigmentosum (XP), and trichothiodystrophy (TTD) <ref>DOI 10.1093/nar/gkv472</ref>. The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation <ref name="Lifuss">PMID: 18510924 </ref>.<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity <ref name="Nance">PMID: 1308368 </ref>. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer. Some XP patients have neurological degeneration. This is possibly due to the fact that neurons do not divide, and mutations that are not corrected by NER accumulate and eventually lead to cell death <ref name="Kraemer">PMID: 17276014 </ref>. TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity <ref name="Hashimoto">PMID: 19808800 </ref>. It has been proposed that specific mutations in XPD helicase affect the transcription activities of TFIIH more than its repair activities, resulting in development issues that lead to intellectual disabilities <ref name="Kraemer">PMID: 17276014 </ref>. Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. Different types of mutations in XPD helicase as well as interactions between XPD helicase defects and defects in other NER proteins can result in these different diseases. Due to the complexity of these interactions, little is known about the molecular basis for the differences in these diseases <ref name="Kraemer">PMID: 17276014 </ref>. <br /> <br /> == Structure Description ==<br /> The structure of the subunit XPD helicase contains one main domain, a DNA interaction interface, and two motifs, one of which performs the function of unwinding the DNA strand. Residues 7-283 form the Helicase ATP binding domain(<scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene>), where ATP itself binds at residues 42-49, (<scene name='72/728075/Nucleotide_binding/3'>ATP Binding</scene>). Interaction with the gene MMS19 is mediated by region consisting of residues 438-637. Residues 234-237 form the motif which is the DEAH box (pertains to a family of proteins that have this region in order to unwind DNA) of this transcription factor which is where the unwinding of DNA is performed. A second motif located at residues 682-695 is where the nuclear localization signal is located. Iron Sulfur bonding residues consist of C116, C134, C155, and C160,(<scene name='72/728075/Iron_sulfur/1'>Iron Sulfur Binding</scene>). Features of Cockayne Syndrome and Xeroderma pigmentosum have been associated with point mutation G602D, and point mutation L461V is associated with TTD1 <ref>DOI 10.1093/nar/gku989 </ref>. <br /> <br /> == Structural highlights ==<br /> <scene name='72/728075/Alpha_helices/4'>Alpha Helices</scene><br /> <br /> <scene name='72/728075/Beta_sheet/3'>Beta Sheets</scene><br /> <br /> <scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene><br /> <br /> <scene name='72/728075/Nucleotide_binding/3'>ATP Binding</scene><br /> <br /> <scene name='72/728075/Iron_sulfur/1'>Iron Sulfur Binding</scene><br /> <br /> <br /> <br /> <br /> == References ==<br /> <references/></div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2588365 XPD Helicase (3CRV) 2016-04-25T17:42:42Z

<p>Bashir Noor: </p> <hr /> <div><StructureSection load='3CRV' size='450' side='right' scene='Journal:BMC:3/Cv/1' caption='XPD helicase, 3CRV'><br /> <br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) helicase is a subunit of Transcription Factor IIH (TFIIH), which aids in transcription initiation and DNA repair. XPD helicse unwinds DNA, allowing other DNA repair enzymes to access and correct damaged regions in the DNA. Because the type of DNA damage that XPD helicase helps to fix is caused by UV light radiation, mutations in XPD helicase results in diseases characterized by light sensitivity. <br /> <br /> == Function ==<br /> XPD helicase is an essential subunit, of the general transcription factor IIH (TFIIH), which is a complex that, along with other general transcription factors, helps to initiate transcription and repair damaged DNA <ref name="Mydikova">PMID: 20429618</ref>. XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme <ref name="Lifuss">PMID: 18510924 </ref>. Helicases, of which XPD helicase is an example, are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes, like polymerases, can act upon the DNA <ref name="Tuteja">PMID: 15128295 </ref>. In the context of DNA repair, helicases unwind DNA, and other enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to ultraviolet (UV) radiation, adjacent nucleotide bases, often thymines, can react and form bulky pyrimidine dimers, which can block enzymes that work on DNA <ref name="Vink">PMID: 11809365 </ref>. For example, during DNA replication, thymine dimers do not fit into the active site of DNA polymerases smoothly, sometimes resulting in mismatched nucleotides. To fix this type of damage on single strands of DNA, cells employ a process called nucleotide excision repair (NER) <ref name="Lifuss">PMID: 18510924 </ref>. This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove the damaged DNA. <br /> <br /> Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP <ref name="Buechner">PMID: 24338567 </ref>. The ATP-dependent helicase activity of XPD helicase, however, is only required for NER, even though TFIIH participates in both repair and transcription initiation <ref name="Kuper">PMID: 25268380 </ref>. XPD helicase not only unravels the DNA around the damage but also helps TFIIH in recognizing bulky lesions in DNA <ref>DOI 10.1093/nar/gkw102 </ref>. The DNA is then threaded through the central pore of XPD helicase, which then opens up the double helix. <br /> <br /> == Disease ==<br /> The NER pathway consists of 28 genes, three of which are part of TFIIH, and mutations in many of these are associated with a set of diseases that are similar but marked differences <ref name="Kraemer">PMID: 17276014 </ref>. Mutations in XPD helicase are associated with three distinct diseases: Cockayne Syndrome (CS), Xeroderma Pigmentosum (XP), and trichothiodystrophy (TTD) <ref>DOI 10.1093/nar/gkv472</ref>. The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation <ref name="Lifuss">PMID: 18510924 </ref>.<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity <ref name="Nance">PMID: 1308368 </ref>. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer. Some XP patients have neurological degeneration. This is possibly due to the fact that neurons do not divide, and mutations that are not corrected by NER accumulate and eventually lead to cell death <ref name="Kraemer">PMID: 17276014 </ref>. TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity <ref name="Hashimoto">PMID: 19808800 </ref>. It has been proposed that specific mutations in XPD helicase affect the transcription activities of TFIIH more than its repair activities, resulting in development issues that lead to intellectual disabilities <ref name="Kraemer">PMID: 17276014 </ref>. Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. Different types of mutations in XPD helicase as well as interactions between XPD helicase defects and defects in other NER proteins can result in these different diseases. Due to the complexity of these interactions, little is known about the molecular basis for the differences in these diseases <ref name="Kraemer">PMID: 17276014 </ref>. <br /> <br /> == Structure Description ==<br /> The structure of the subunit XPD helicase contains one main domain, a DNA interaction interface, and two motifs, one of which performs the function of unwinding the DNA strand. Residues 7-283 form the Helicase ATP binding domain(<scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene>), where ATP itself binds at residues 42-49, (<scene name='72/728075/Nucleotide_binding/3'>ATP Binding</scene>). Interaction with the gene MMS19 is mediated by region consisting of residues 438-637. Residues 234-237 form the motif which is the DEAH box (pertains to a family of proteins that have this region in order to unwind DNA) of this transcription factor which is where the unwinding of DNA is performed. A second motif located at residues 682-695 is where the nuclear localization signal is located. Iron Sulfur bonding residues consist of C116, C134, C155, and C160. Features of Cockayne Syndrome and Xeroderma pigmentosum have been associated with point mutation G602D, and point mutation L461V is associated with TTD1 <ref>DOI 10.1093/nar/gku989 </ref>. <br /> <br /> == Structural highlights ==<br /> <scene name='72/728075/Alpha_helices/4'>Alpha Helices</scene><br /> <br /> <scene name='72/728075/Beta_sheet/3'>Beta Sheets</scene><br /> <br /> <scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene><br /> <br /> <scene name='72/728075/Nucleotide_binding/3'>ATP Binding</scene><br /> <br /> <br /> <br /> <br /> == References ==<br /> <references/></div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2588323 XPD Helicase (3CRV) 2016-04-24T21:12:55Z

<p>Bashir Noor: </p> <hr /> <div><StructureSection load='3CRV' size='450' side='right' scene='Journal:BMC:3/Cv/1' caption='XPD helicase, 3CRV'><br /> <br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) helicase is a subunit of Transcription Factor II Human (TFIIH), which aids in DNA repair. XPD helicse unwinds DNA, allowing other DNA repair enzymes to access and correct damaged regions in the DNA. Because the type of DNA damage that XPD helicase helps to fix is caused by UV light radiation, mutations in XPD helicase results in diseases characterized by light sensitivity. <br /> <br /> == Function ==<br /> XPD helicase is an essential subunit, of the general transcription factor IIH (TFIIH), which is a complex that, along with other general transcription factors, help to initiate transcription and repair damaged DNA <ref name="Mydikova">PMID: 20429618</ref>. XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme <ref name="Lifuss">PMID: 18510924 </ref>. Helicases, of which XPD helicase is an example, are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes, like polymerases, can act upon the DNA <ref name="Tuteja">PMID: 15128295 </ref>. In the context of DNA repair, helicases unwind DNA, and other enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to ultraviolet (UV) radiation, adjacent nucleotide bases, often thymines, can react and form bulky pyrimidine dimers, which can block enzymes that work on DNA <ref name="Vink">PMID: 11809365 </ref>. For example, during DNA replication, thymine dimers do not fit into the active site of DNA polymerases smoothly, sometimes resulting in mismatched nucleotides. To fix this type of damage on single strands of DNA, cells employ a process called nucleotide excision repair (NER) <ref name="Lifuss">PMID: 18510924 </ref>. This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove the damaged DNA. <br /> <br /> Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP <ref name="Buechner">PMID: 24338567 </ref>. The ATP-dependent helicase activity of XPD helicase, however, is only required for NER, even though TFIIH participates in both repair and transcription initiation <ref name="Kuper">PMID: 25268380 </ref>. XPD helicase not only unravels the DNA around the damage but also helps TFIIH in recognizing bulky lesions in DNA <ref>DOI 10.1093/nar/gkw102 </ref>. The DNA is then threaded through the central pore of XPD helicase, which then opens up the double helix. <br /> <br /> == Disease ==<br /> Mutations in XPD helicase are associated with three distinct diseases: Cockayne Syndrome (CS), Xeroderma Pigmentosum (XP), and trichothiodystrophy (TTD) <ref>DOI 10.1093/nar/gkv472</ref>. The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation <ref name="Lifuss">PMID: 18510924 </ref>.<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity <ref name="Nance">PMID: 1308368 </ref>. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer . TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity <ref name="Hashimoto">PMID: 19808800 </ref>. Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. <br /> <br /> == Structure Description ==<br /> The structure of the subunit XPD helicase contains one main domain, a DNA interaction interface, and two motifs, one of which performs the function of unwinding the DNA strand. Residues 7-283 form the Helicase ATP binding domain. Interaction with the gene MMS19 is mediated by region consisting of residues 438-637. Residues 234-237 form the motif which is the DEAH box (pertains to a family of proteins that have this region in order to unwind DNA) of this transcription factor which is where the unwinding of DNA is performed. A second motif located at residues 682-695 is where the nuclear localization signal is located. Iron Sulfur bonding residues consist of C116, C134, C155, and C160. Features of Cockayne Syndrome and Xeroderma pigmentosum have been associated with point mutation G602D, and point mutation L461V is associated with TTD1 <ref>DOI 10.1093/nar/gku989 </ref>. <br /> <br /> == Structural highlights ==<br /> <scene name='72/728075/Alpha_helices/4'>Alpha Helices</scene><br /> <br /> <scene name='72/728075/Beta_sheet/3'>Beta Sheets</scene><br /> <br /> <scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene><br /> <br /> <scene name='72/728075/Nucleotide_binding/3'>ATP Binding</scene><br /> <br /> <br /> <br /> <br /> == References ==<br /> <references/></div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2588320 XPD Helicase (3CRV) 2016-04-24T21:02:09Z

<p>Bashir Noor: </p> <hr /> <div><StructureSection load='3CRV' size='450' side='right' scene='Journal:BMC:3/Cv/1' caption='XPD helicase, 3CRV'><br /> <br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) helicase is a subunit of Transcription Factor II Human (TFIIH), which aids in DNA repair. XPD helicse unwinds DNA, allowing other DNA repair enzymes to access and correct damaged regions in the DNA. Because the type of DNA damage that XPD helicase helps to fix is caused by UV light radiation, mutations in XPD helicase results in diseases characterized by light sensitivity. <br /> <br /> == Function ==<br /> XPD helicase is an essential subunit, of the general transcription factor IIH (TFIIH), which is a complex that, along with other general transcription factors, help to initiate transcription and repair damaged DNA <ref name="Mydikova">PMID: 20429618</ref>. XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme <ref name="Lifuss">PMID: 18510924 </ref>. Helicases, of which XPD helicase is an example, are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes, like polymerases, can act upon the DNA <ref name="Tuteja">PMID: 15128295 </ref>. In the context of DNA repair, helicases unwind DNA, and other enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to ultraviolet (UV) radiation, adjacent nucleotide bases, often thymines, can react and form bulky pyrimidine dimers, which can block enzymes that work on DNA <ref name="Vink">PMID: 11809365 </ref>. For example, during DNA replication, thymine dimers do not fit into the active site of DNA polymerases smoothly, sometimes resulting in mismatched nucleotides. To fix this type of damage on single strands of DNA, cells employ a process called nucleotide excision repair (NER) <ref name="Lifuss">PMID: 18510924 </ref>. This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove the damaged DNA. <br /> <br /> Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP <ref name="Buechner">PMID: 24338567 </ref>. The ATP-dependent helicase activity of XPD helicase, however, is only required for NER, even though TFIIH participates in both repair and transcription initiation <ref name="Kuper">PMID: 25268380 </ref>. XPD helicase not only unravels the DNA around the damage but also helps TFIIH in recognizing bulky lesions in DNA <ref>DOI 10.1093/nar/gkw102 </ref>. The DNA is then threaded through the central pore of XPD helicase, which then opens up the double helix. <br /> <br /> == Disease ==<br /> Mutations in XPD helicase are associated with three distinct diseases: Cockayne Syndrome (CS), Xeroderma Pigmentosum (XP), and trichothiodystrophy (TTD) <ref>DOI 10.1093/nar/gkv472</ref>. The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation <ref name="Lifuss">PMID: 18510924 </ref>.<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity <ref name="Nance">PMID: 1308368 </ref>. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer . TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity <ref name="Hashimoto">PMID: 19808800 </ref>. Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. <br /> <br /> == Structure Description ==<br /> Residues 7-283 form the Helicase ATP binding domain. Interaction with the gene MMS19 is mediated by region consisting of residues 438-637. Residues 234-237 form the motif which is the DEAH box of this transcription factor. A second motif located at residues 682-695 is where the nuclear localization signal is located. Iron Sulfur bonding residues consist of C116, C134, C155, and C160. Features of Cockayne Syndrome and Xeroderma pigmentosum have been associated with point mutation G602D, and point mutation L461V is associated with TTD1 <ref>DOI 10.1093/nar/gku989 </ref>. <br /> <br /> == Structural highlights ==<br /> <scene name='72/728075/Alpha_helices/4'>Alpha Helices</scene><br /> <br /> <scene name='72/728075/Beta_sheet/3'>Beta Sheets</scene><br /> <br /> <scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene><br /> <br /> <scene name='72/728075/Nucleotide_binding/3'>ATP Binding</scene><br /> <br /> <br /> <br /> <br /> == References ==<br /> <references/></div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2588319 XPD Helicase (3CRV) 2016-04-24T20:48:43Z

<p>Bashir Noor: </p> <hr /> <div><StructureSection load='3CRV' size='450' side='right' scene='Journal:BMC:3/Cv/1' caption='XPD helicase, 3CRV'><br /> <br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) helicase is a subunit of Transcription Factor II Human (TFIIH), which aids in DNA repair. XPD helicse unwinds DNA, allowing other DNA repair enzymes to access and correct damaged regions in the DNA. Because the type of DNA damage that XPD helicase helps to fix is caused by UV light radiation, mutations in XPD helicase results in diseases characterized by light sensitivity. <br /> <br /> == Function ==<br /> XPD helicase is an essential subunit, of the general transcription factor IIH (TFIIH), which is a complex that, along with other general transcription factors, help to initiate transcription and repair damaged DNA <ref name="Mydikova">PMID: 20429618</ref>. XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme <ref name="Lifuss">PMID: 18510924 </ref>. Helicases, of which XPD helicase is an example, are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes, like polymerases, can act upon the DNA <ref name="Tuteja">PMID: 15128295 </ref>. In the context of DNA repair, helicases unwind DNA, and other enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to ultraviolet (UV) radiation, adjacent nucleotide bases, often thymines, can react and form bulky pyrimidine dimers, which can block enzymes that work on DNA <ref name="Vink">PMID: 11809365 </ref>. For example, during DNA replication, thymine dimers do not fit into the active site of DNA polymerases smoothly, sometimes resulting in mismatched nucleotides. To fix this type of damage on single strands of DNA, cells employ a process called nucleotide excision repair (NER) <ref name="Lifuss">PMID: 18510924 </ref>. This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove the damaged DNA. <br /> <br /> Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP <ref name="Buechner">PMID: 24338567 </ref>. The ATP-dependent helicase activity of XPD helicase, however, is only required for NER, even though TFIIH participates in both repair and transcription initiation <ref name="Kuper">PMID: 25268380 </ref>. XPD helicase not only unravels the DNA around the damage but also helps TFIIH in recognizing bulky lesions in DNA <ref>DOI 10.1093/nar/gkw102 </ref>. The DNA is then threaded through the central pore of XPD helicase, which then opens up the double helix. <br /> <br /> == Disease ==<br /> Mutations in XPD helicase are associated with three distinct diseases: Cockayne Syndrome (CS), Xeroderma Pigmentosum (XP), and trichothiodystrophy (TTD) <ref>DOI 10.1093/nar/gkv472</ref>. The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation <ref name="Lifuss">PMID: 18510924 </ref>.<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity <ref name="Nance">PMID: 1308368 </ref>. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer . TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity <ref name="Hashimoto">PMID: 19808800 </ref>. Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. <br /> <br /> == Structure Description ==<br /> Residues 7-283 form the Helicase ATP binding domain. Interaction with the gene MMS19 is mediated by region consisting of residues 438-637. Residues 234-237 form the motif which is the DEAH box of this transcription factor. A second motif located at residues 682-695 is where the nuclear localization signal is located. Iron Sulfur bonding residues consist of C116, C134, C155, and C160. <ref>DOI 10.1093/nar/gku989 </ref>. <br /> <br /> == Structural highlights ==<br /> <scene name='72/728075/Alpha_helices/4'>Alpha Helices</scene><br /> <br /> <scene name='72/728075/Beta_sheet/3'>Beta Sheets</scene><br /> <br /> <scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene><br /> <br /> <scene name='72/728075/Nucleotide_binding/3'>ATP Binding</scene><br /> <br /> <br /> <br /> <br /> == References ==<br /> <references/></div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2588313 XPD Helicase (3CRV) 2016-04-24T20:17:53Z

<p>Bashir Noor: </p> <hr /> <div><StructureSection load='3CRV' size='450' side='right' scene='Journal:BMC:3/Cv/1' caption='XPD helicase, 3CRV'><br /> <br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) helicase is a subunit of Transcription Factor II Human (TFIIH), which aids in DNA repair.<ref >doi 10.1016/j.bmc.2012.03.019</ref> XPD helicse unwinds DNA, allowing other DNA repair enzymes to access and correct damaged regions in the DNA. Because the type of DNA damage that XPD helicase helps to fix is caused by UV light radiation, mutations in XPD helicase results in diseases characterized by light sensitivity. <br /> <br /> == Function ==<br /> XPD helicase is an essential subunit, of the general transcription factor IIH (TFIIH), which is a complex that, along with other general transcription factors, help to initiate transcription and repair damaged DNA (1). XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme (2). Helicases, of which XPD helicase is an example, are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes, like polymerases, can act upon the DNA (3). In the context of DNA repair, helicases unwind DNA, and other enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to ultraviolet (UV) radiation, adjacent nucleotide bases, often thymines, can react and form bulky pyrimidine dimers, which can block enzymes that work on DNA (4). For example, during DNA replication, thymine dimers do not fit into the active site of DNA polymerases smoothly, sometimes resulting in mismatched nucleotides. To fix this type of damage on single strands of DNA, cells employ a process called nucleotide excision repair (NER) (2). This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove the damaged DNA. <br /> <br /> Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP (5). The ATP-dependent helicase activity of XPD helicase, however, is only required for NER, even though TFIIH participates in both repair and transcription initiation (6). XPD helicase not only unravels the DNA around the damage but also helps TFIIH in recognizing bulky lesions in DNA (7). The DNA is then threaded through the central pore of XPD helicase, which then opens up the double helix. <br /> <br /> == Disease ==<br /> Mutations in XPD helicase are associated with three distinct diseases: Cockayne Syndrome (CS), Xeroderma Pigmentosum (XP), and trichothiodystrophy (TTD) (7). The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation (2).<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity (8). XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer (9). TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity (10). Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. <br /> <br /> == Structure Description ==<br /> Residues 7-283 form the Helicase ATP binding domain. Interaction with the gene MMS19 is mediated by region consisting of residues 438-637. Residues 234-237 form the motif which is the DEAH box of this transcription factor. A second motif located at residues 682-695 is where the nuclear localization signal is located. <br /> <br /> == Structural highlights ==<br /> <scene name='72/728075/Alpha_helices/4'>Alpha Helices</scene><br /> <br /> <scene name='72/728075/Beta_sheet/3'>Beta Sheets</scene><br /> <br /> <scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene><br /> <br /> <scene name='72/728075/Nucleotide_binding/3'>ATP Binding</scene><br /> <br /> <br /> <br /> <br /> == References ==<br /> <references/><br /> # Mydilkova, Z., Gursky, J., Piersel, M. (2010) Transcription factor IIH- the protein complex with multiple functions, Neoplasm 57, 287-290.<br /> # Li, F., Fuss, J., Cheng, Q., Arvai, A., Hammel, M., Roberts, V., Cooper, P., Tainer, J. (2008) XPD helicase structures and activities: Insights into the cancer and aging phenotypes from XPD mutations, Cell 133, 789-800.<br /> # Tuteja, N., Tuteja, R. (2004) Unraveling DNA helicases: Motif, structure, mechanism and function, Eur J Biochem 271, 1849-1863.<br /> # Vink, A., Roza, L. (2001) Biological consequences of cyclobutane pyrimidine dimers, Journal of Photochemistry and Photobiology, 65, 101-104.<br /> # Buechner, C., Heil, K., Michels, G., Carell, T., Kisker, C., Tessmer, I. (2014) Strand-specific recognition of DNA damages by XPD provides insights into nucleotide excision repair substrate versatility, J Biol Chem, 289, 3613-3624.<br /> # Kuper, J., Braun, C., Elias, A., Michels, G., Sauer, F., Schmitt, D., Poterszman, A., Egly, J., Kisker., C. (2014) PLoS Biol., 12. doi: 10.1371/journal.pbio.1001954.<br /> # Constantinescu-Aruxandei, D., Petrovic-Stojanovska, B., Penedo, J., White, M., Naismith, J. (2016) Mechanism of DNA loading by the DNA repair helicase XPD, Nucl. Acids Res., 44, 2806-2815.<br /> # Nance MA, Berry SA. (1992) Cockayne syndrome: review of 140 cases, Am J Med Genet 42, 68-84. Review.<br /> # Hengge UR, Emmert S. (2008) Clinical features of xeroderma pigmentosum, Adv Exp Med Biol. 637, 10-8. Review.<br /> # Hashimoto S, Egly JM. (2009) Trichothiodystrophy view from the molecular basis of DNA repair/transcription factor TFIIH, Hum Mol Genet. 18, R224-30. doi: 10.1093/hmg/ddp390. Review.</div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2588312 XPD Helicase (3CRV) 2016-04-24T20:15:52Z

<p>Bashir Noor: </p> <hr /> <div><StructureSection load='3CRV' size='450' side='right' scene='Journal:BMC:3/Cv/1' caption='XPD helicase, 3CRV'><br /> <br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) helicase is a subunit of Transcription Factor II Human (TFIIH), which aids in DNA repair.<ref >doi 10.1016/j.bmc.2012.03.019</ref> XPD helicse unwinds DNA, allowing other DNA repair enzymes to access and correct damaged regions in the DNA. Because the type of DNA damage that XPD helicase helps to fix is caused by UV light radiation, mutations in XPD helicase results in diseases characterized by light sensitivity. <br /> <br /> == Function ==<br /> XPD helicase is an essential subunit, of the general transcription factor IIH (TFIIH), which is a complex that, along with other general transcription factors, help to initiate transcription and repair damaged DNA (1). XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme (2). Helicases, of which XPD helicase is an example, are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes, like polymerases, can act upon the DNA (3). In the context of DNA repair, helicases unwind DNA, and other enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to ultraviolet (UV) radiation, adjacent nucleotide bases, often thymines, can react and form bulky pyrimidine dimers, which can block enzymes that work on DNA (4). For example, during DNA replication, thymine dimers do not fit into the active site of DNA polymerases smoothly, sometimes resulting in mismatched nucleotides. To fix this type of damage on single strands of DNA, cells employ a process called nucleotide excision repair (NER) (2). This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove the damaged DNA. <br /> <br /> Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP (5). The ATP-dependent helicase activity of XPD helicase, however, is only required for NER, even though TFIIH participates in both repair and transcription initiation (6). XPD helicase not only unravels the DNA around the damage but also helps TFIIH in recognizing bulky lesions in DNA (7). The DNA is then threaded through the central pore of XPD helicase, which then opens up the double helix. <br /> <br /> == Disease ==<br /> Mutations in XPD helicase are associated with three distinct diseases: Cockayne Syndrome (CS), Xeroderma Pigmentosum (XP), and trichothiodystrophy (TTD) (7). The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation (2).<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity (8). XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer (9). TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity (10). Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. <br /> <br /> == Structure Description ==<br /> Residues 7-283 form the Helicase ATP binding domain. Interaction with the gene MMS19 is mediated by region consisting of residues 438-637. Residues 234-237 form the motif which is the DEAH box of this transcription factor. A second motif located at residues 682-695 is where the nuclear localization signal. <br /> <br /> == Structural highlights ==<br /> <scene name='72/728075/Alpha_helices/4'>Alpha Helices</scene><br /> <br /> <scene name='72/728075/Beta_sheet/3'>Beta Sheets</scene><br /> <br /> <scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene><br /> <br /> <scene name='72/728075/Nucleotide_binding/3'>ATP Binding</scene><br /> <br /> <br /> <br /> <br /> == References ==<br /> <references/><br /> # Mydilkova, Z., Gursky, J., Piersel, M. (2010) Transcription factor IIH- the protein complex with multiple functions, Neoplasm 57, 287-290.<br /> # Li, F., Fuss, J., Cheng, Q., Arvai, A., Hammel, M., Roberts, V., Cooper, P., Tainer, J. (2008) XPD helicase structures and activities: Insights into the cancer and aging phenotypes from XPD mutations, Cell 133, 789-800.<br /> # Tuteja, N., Tuteja, R. (2004) Unraveling DNA helicases: Motif, structure, mechanism and function, Eur J Biochem 271, 1849-1863.<br /> # Vink, A., Roza, L. (2001) Biological consequences of cyclobutane pyrimidine dimers, Journal of Photochemistry and Photobiology, 65, 101-104.<br /> # Buechner, C., Heil, K., Michels, G., Carell, T., Kisker, C., Tessmer, I. (2014) Strand-specific recognition of DNA damages by XPD provides insights into nucleotide excision repair substrate versatility, J Biol Chem, 289, 3613-3624.<br /> # Kuper, J., Braun, C., Elias, A., Michels, G., Sauer, F., Schmitt, D., Poterszman, A., Egly, J., Kisker., C. (2014) PLoS Biol., 12. doi: 10.1371/journal.pbio.1001954.<br /> # Constantinescu-Aruxandei, D., Petrovic-Stojanovska, B., Penedo, J., White, M., Naismith, J. (2016) Mechanism of DNA loading by the DNA repair helicase XPD, Nucl. Acids Res., 44, 2806-2815.<br /> # Nance MA, Berry SA. (1992) Cockayne syndrome: review of 140 cases, Am J Med Genet 42, 68-84. Review.<br /> # Hengge UR, Emmert S. (2008) Clinical features of xeroderma pigmentosum, Adv Exp Med Biol. 637, 10-8. Review.<br /> # Hashimoto S, Egly JM. (2009) Trichothiodystrophy view from the molecular basis of DNA repair/transcription factor TFIIH, Hum Mol Genet. 18, R224-30. doi: 10.1093/hmg/ddp390. Review.</div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2588310 XPD Helicase (3CRV) 2016-04-24T20:03:51Z

<p>Bashir Noor: </p> <hr /> <div><StructureSection load='3CRV' size='450' side='right' scene='Journal:BMC:3/Cv/1' caption='XPD helicase, 3CRV'><br /> <br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) is a subunit of Transcription Factor II Human (TFIIH).<ref >doi 10.1016/j.bmc.2012.03.019</ref><br /> <br /> == Function ==<br /> XPD helicase is an essential subunit, of the general transcription factor IIH (TFIIH), which is a complex that, along with other general transcription factors, help to initiate transcription and repair damaged DNA (1). XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme (2). Helicases, of which XPD helicase is an example, are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes, like polymerases, can act upon the DNA (3). In the context of DNA repair, helicases unwind DNA, and other enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to ultraviolet (UV) radiation, adjacent nucleotide bases, often thymines, can react and form bulky pyrimidine dimers, which can block enzymes that work on DNA (4). For example, during DNA replication, thymine dimers do not fit into the active site of DNA polymerases smoothly, sometimes resulting in mismatched nucleotides. To fix this type of damage on single strands of DNA, cells employ a process called nucleotide excision repair (NER) (2). This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove the damaged DNA. <br /> <br /> Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP (5). The ATP-dependent helicase activity of XPD helicase, however, is only required for NER, even though TFIIH participates in both repair and transcription initiation (6). XPD helicase not only unravels the DNA around the damage but also helps TFIIH in recognizing bulky lesions in DNA (7). The DNA is then threaded through the central pore of XPD helicase, which then opens up the double helix. <br /> <br /> == Disease ==<br /> Mutations in XPD helicase are associated with three distinct diseases: Cockayne Syndrome (CS), Xeroderma Pigmentosum (XP), and trichothiodystrophy (TTD) (7). The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation (2).<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity (8). XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer (9). TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity (10). Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. <br /> <br /> == Structure Description ==<br /> Residues 7-283 form the Helicase ATP binding domain. Interaction with the gene MMS19 is mediated by region consisting of residues 438-637. <br /> <br /> == Structural highlights ==<br /> <scene name='72/728075/Alpha_helices/4'>Alpha Helices</scene><br /> <br /> <scene name='72/728075/Beta_sheet/3'>Beta Sheets</scene><br /> <br /> <scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene><br /> <br /> <scene name='72/728075/Nucleotide_binding/3'>ATP Binding</scene><br /> <br /> <br /> <br /> <br /> == References ==<br /> <references/><br /> # Mydilkova, Z., Gursky, J., Piersel, M. (2010) Transcription factor IIH- the protein complex with multiple functions, Neoplasm 57, 287-290.<br /> # Li, F., Fuss, J., Cheng, Q., Arvai, A., Hammel, M., Roberts, V., Cooper, P., Tainer, J. (2008) XPD helicase structures and activities: Insights into the cancer and aging phenotypes from XPD mutations, Cell 133, 789-800.<br /> # Tuteja, N., Tuteja, R. (2004) Unraveling DNA helicases: Motif, structure, mechanism and function, Eur J Biochem 271, 1849-1863.<br /> # Vink, A., Roza, L. (2001) Biological consequences of cyclobutane pyrimidine dimers, Journal of Photochemistry and Photobiology, 65, 101-104.<br /> # Buechner, C., Heil, K., Michels, G., Carell, T., Kisker, C., Tessmer, I. (2014) Strand-specific recognition of DNA damages by XPD provides insights into nucleotide excision repair substrate versatility, J Biol Chem, 289, 3613-3624.<br /> # Kuper, J., Braun, C., Elias, A., Michels, G., Sauer, F., Schmitt, D., Poterszman, A., Egly, J., Kisker., C. (2014) PLoS Biol., 12. doi: 10.1371/journal.pbio.1001954.<br /> # Constantinescu-Aruxandei, D., Petrovic-Stojanovska, B., Penedo, J., White, M., Naismith, J. (2016) Mechanism of DNA loading by the DNA repair helicase XPD, Nucl. Acids Res., 44, 2806-2815.<br /> # Nance MA, Berry SA. (1992) Cockayne syndrome: review of 140 cases, Am J Med Genet 42, 68-84. Review.<br /> # Hengge UR, Emmert S. (2008) Clinical features of xeroderma pigmentosum, Adv Exp Med Biol. 637, 10-8. Review.<br /> # Hashimoto S, Egly JM. (2009) Trichothiodystrophy view from the molecular basis of DNA repair/transcription factor TFIIH, Hum Mol Genet. 18, R224-30. doi: 10.1093/hmg/ddp390. Review.</div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2588309 XPD Helicase (3CRV) 2016-04-24T20:01:20Z

<p>Bashir Noor: </p> <hr /> <div><StructureSection load='3CRV' size='450' side='right' scene='Journal:BMC:3/Cv/1' caption='XPD helicase, 3CRV'><br /> <br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) is a subunit of Transcription Factor II Human (TFIIH).<ref >doi 10.1016/j.bmc.2012.03.019</ref><br /> <br /> == Function ==<br /> XPD helicase is an essential subunit, of the general transcription factor IIH (TFIIH), which is a complex that, along with other general transcription factors, help to initiate transcription and repair damaged DNA (1). XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme (2). Helicases, of which XPD helicase is an example, are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes, like polymerases, can act upon the DNA (3). In the context of DNA repair, helicases unwind DNA, and other enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to ultraviolet (UV) radiation, adjacent nucleotide bases, often thymines, can react and form bulky pyrimidine dimers, which can block enzymes that work on DNA (4). For example, during DNA replication, thymine dimers do not fit into the active site of DNA polymerases smoothly, sometimes resulting in mismatched nucleotides. To fix this type of damage on single strands of DNA, cells employ a process called nucleotide excision repair (NER) (2). This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove the damaged DNA. <br /> <br /> Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP (5). The ATP-dependent helicase activity of XPD helicase, however, is only required for NER, even though TFIIH participates in both repair and transcription initiation (6). XPD helicase not only unravels the DNA around the damage but also helps TFIIH in recognizing bulky lesions in DNA (7). The DNA is then threaded through the central pore of XPD helicase, which then opens up the double helix. <br /> <br /> == Disease ==<br /> Mutations in XPD helicase are associated with three distinct diseases: Cockayne Syndrome (CS), Xeroderma Pigmentosum (XP), and trichothiodystrophy (TTD) (7). The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation (2).<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity (8). XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer (9). TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity (10). Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. <br /> <br /> == Structure Description ==<br /> Residues 7-283 form the Helicase ATP binding domain. <br /> == Structural highlights ==<br /> <scene name='72/728075/Alpha_helices/4'>Alpha Helices</scene><br /> <br /> <scene name='72/728075/Beta_sheet/3'>Beta Sheets</scene><br /> <br /> <scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene><br /> <br /> <scene name='72/728075/Nucleotide_binding/3'>ATP Binding</scene><br /> <br /> <br /> <br /> <br /> == References ==<br /> <references/><br /> # Mydilkova, Z., Gursky, J., Piersel, M. (2010) Transcription factor IIH- the protein complex with multiple functions, Neoplasm 57, 287-290.<br /> # Li, F., Fuss, J., Cheng, Q., Arvai, A., Hammel, M., Roberts, V., Cooper, P., Tainer, J. (2008) XPD helicase structures and activities: Insights into the cancer and aging phenotypes from XPD mutations, Cell 133, 789-800.<br /> # Tuteja, N., Tuteja, R. (2004) Unraveling DNA helicases: Motif, structure, mechanism and function, Eur J Biochem 271, 1849-1863.<br /> # Vink, A., Roza, L. (2001) Biological consequences of cyclobutane pyrimidine dimers, Journal of Photochemistry and Photobiology, 65, 101-104.<br /> # Buechner, C., Heil, K., Michels, G., Carell, T., Kisker, C., Tessmer, I. (2014) Strand-specific recognition of DNA damages by XPD provides insights into nucleotide excision repair substrate versatility, J Biol Chem, 289, 3613-3624.<br /> # Kuper, J., Braun, C., Elias, A., Michels, G., Sauer, F., Schmitt, D., Poterszman, A., Egly, J., Kisker., C. (2014) PLoS Biol., 12. doi: 10.1371/journal.pbio.1001954.<br /> # Constantinescu-Aruxandei, D., Petrovic-Stojanovska, B., Penedo, J., White, M., Naismith, J. (2016) Mechanism of DNA loading by the DNA repair helicase XPD, Nucl. Acids Res., 44, 2806-2815.<br /> # Nance MA, Berry SA. (1992) Cockayne syndrome: review of 140 cases, Am J Med Genet 42, 68-84. Review.<br /> # Hengge UR, Emmert S. (2008) Clinical features of xeroderma pigmentosum, Adv Exp Med Biol. 637, 10-8. Review.<br /> # Hashimoto S, Egly JM. (2009) Trichothiodystrophy view from the molecular basis of DNA repair/transcription factor TFIIH, Hum Mol Genet. 18, R224-30. doi: 10.1093/hmg/ddp390. Review.</div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2588303 XPD Helicase (3CRV) 2016-04-24T19:40:28Z

<p>Bashir Noor: </p> <hr /> <div><StructureSection load='3CRV' size='450' side='right' scene='Journal:BMC:3/Cv/1' caption='XPD helicase, 3CRV'><br /> <br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) is a subunit of Transcription Factor II Human (TFIIH).<br /> <br /> == Function ==<br /> XPD helicase is an essential part, or subunit, of the general transcription factor IIH (TFIIH), which is a complex that, along with other general transcription factors, help to initiate transcription and repair damaged DNA (1). XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme (2). Helicases, of which XPD helicase is a type, are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes, like polymerases, can act upon the DNA (3). In the context of DNA repair, these enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to ultraviolet (UV) radiation, adjacent nucleotide bases, often thymines, can react and form bulky pyrimidine dimers, which can block enzymes that work on DNA (4). For example, during DNA replication, dimers do not fit into the active site of DNA polymerases smoothly, sometimes resulting in mismatched nucleotides. To fix this type of damage on single strands of DNA, cells employ a process called nucleotide excision repair (NER) (2). This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove the damaged DNA. <br /> <br /> Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP (5). The ATP-dependent helicase activity of XPD helicase, however, is only required for NER, even though TFIIH participates in both repair and transcription initiation (6). XPD helicase not only unravels the DNA around the damage but also helps TFIIH in recognizing bulky lesions in DNA (7). The DNA is then threaded through the central pore of XPD helicase, which then opens up the double helix. <br /> <br /> == Disease ==<br /> Mutations in XPD helicase are associated with three distinct diseases: Cockayne Syndrome (CS), Xeroderma Pigmentosum (XP), and trichothiodystrophy (TTD) (7). The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation (2).<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity (8). XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer (9). TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity (10). Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. <br /> <br /> == Structure Description ==<br /> <br /> == Structural highlights ==<br /> <scene name='72/728075/Alpha_helices/4'>Alpha Helices</scene><br /> <br /> <scene name='72/728075/Beta_sheet/3'>Beta Sheets</scene><br /> <br /> <scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene><br /> <br /> <scene name='72/728075/Nucleotide_binding/3'>ATP Binding</scene><br /> <br /> <br /> <br /> <br /> == References ==<br /> <references/><br /> # Mydilkova, Z., Gursky, J., Piersel, M. (2010) Transcription factor IIH- the protein complex with multiple functions, Neoplasm 57, 287-290.<br /> # Li, F., Fuss, J., Cheng, Q., Arvai, A., Hammel, M., Roberts, V., Cooper, P., Tainer, J. (2008) XPD helicase structures and activities: Insights into the cancer and aging phenotypes from XPD mutations, Cell 133, 789-800.<br /> # Tuteja, N., Tuteja, R. (2004) Unraveling DNA helicases: Motif, structure, mechanism and function, Eur J Biochem 271, 1849-1863.<br /> # Vink, A., Roza, L. (2001) Biological consequences of cyclobutane pyrimidine dimers, Journal of Photochemistry and Photobiology, 65, 101-104.<br /> # Buechner, C., Heil, K., Michels, G., Carell, T., Kisker, C., Tessmer, I. (2014) Strand-specific recognition of DNA damages by XPD provides insights into nucleotide excision repair substrate versatility, J Biol Chem, 289, 3613-3624.<br /> # Kuper, J., Braun, C., Elias, A., Michels, G., Sauer, F., Schmitt, D., Poterszman, A., Egly, J., Kisker., C. (2014) PLoS Biol., 12. doi: 10.1371/journal.pbio.1001954.<br /> # Constantinescu-Aruxandei, D., Petrovic-Stojanovska, B., Penedo, J., White, M., Naismith, J. (2016) Mechanism of DNA loading by the DNA repair helicase XPD, Nucl. Acids Res., 44, 2806-2815.<br /> # Nance MA, Berry SA. (1992) Cockayne syndrome: review of 140 cases, Am J Med Genet 42, 68-84. Review.<br /> # Hengge UR, Emmert S. (2008) Clinical features of xeroderma pigmentosum, Adv Exp Med Biol. 637, 10-8. Review.<br /> # Hashimoto S, Egly JM. (2009) Trichothiodystrophy view from the molecular basis of DNA repair/transcription factor TFIIH, Hum Mol Genet. 18, R224-30. doi: 10.1093/hmg/ddp390. Review.</div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2588302 XPD Helicase (3CRV) 2016-04-24T19:40:27Z

<p>Bashir Noor: </p> <hr /> <div><StructureSection load='3CRV' size='450' side='right' scene='Journal:BMC:3/Cv/1' caption='XPD helicase, 3CRV'><br /> <br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) is a subunit of Transcription Factor II Human (TFIIH).<br /> <br /> == Function ==<br /> XPD helicase is an essential subunit of the general transcription factor IIH (TFIIH), which is a complex that, along with other general transcription factors, help to initiate transcription and repair damaged DNA (1). XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme (2). Helicases, of which XPD helicase is an example, are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes, like polymerases, can act upon the DNA (3). In the context of DNA repair, these enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to ultraviolet (UV) radiation, adjacent nucleotide bases, often thymines, can react and form bulky pyrimidine dimers, which can block enzymes that work on DNA (4). For example, during DNA replication, thymine dimers do not fit into the active site of DNA polymerases smoothly, sometimes resulting in mismatched nucleotides. To fix this type of damage on single strands of DNA, cells employ a process called nucleotide excision repair (NER) (2). This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove the damaged DNA. <br /> <br /> Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP (5). The ATP-dependent helicase activity of XPD helicase, however, is only required for NER, even though TFIIH participates in both repair and transcription initiation (6). XPD helicase not only unravels the DNA around the damage but also helps TFIIH in recognizing bulky lesions in DNA (7). The DNA is then threaded through the central pore of XPD helicase, which then opens up the double helix. <br /> <br /> == Disease ==<br /> Mutations in XPD helicase are associated with three distinct diseases: Cockayne Syndrome (CS), Xeroderma Pigmentosum (XP), and trichothiodystrophy (TTD) (7). The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation (2).<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity (8). XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer (9). TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity (10). Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. <br /> <br /> == Structure Description ==<br /> <br /> == Structural highlights ==<br /> <scene name='72/728075/Alpha_helices/4'>Alpha Helices</scene><br /> <br /> <scene name='72/728075/Beta_sheet/3'>Beta Sheets</scene><br /> <br /> <scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene><br /> <br /> <scene name='72/728075/Nucleotide_binding/3'>ATP Binding</scene><br /> <br /> <br /> <br /> <br /> == References ==<br /> <references/><br /> # Mydilkova, Z., Gursky, J., Piersel, M. (2010) Transcription factor IIH- the protein complex with multiple functions, Neoplasm 57, 287-290.<br /> # Li, F., Fuss, J., Cheng, Q., Arvai, A., Hammel, M., Roberts, V., Cooper, P., Tainer, J. (2008) XPD helicase structures and activities: Insights into the cancer and aging phenotypes from XPD mutations, Cell 133, 789-800.<br /> # Tuteja, N., Tuteja, R. (2004) Unraveling DNA helicases: Motif, structure, mechanism and function, Eur J Biochem 271, 1849-1863.<br /> # Vink, A., Roza, L. (2001) Biological consequences of cyclobutane pyrimidine dimers, Journal of Photochemistry and Photobiology, 65, 101-104.<br /> # Buechner, C., Heil, K., Michels, G., Carell, T., Kisker, C., Tessmer, I. (2014) Strand-specific recognition of DNA damages by XPD provides insights into nucleotide excision repair substrate versatility, J Biol Chem, 289, 3613-3624.<br /> # Kuper, J., Braun, C., Elias, A., Michels, G., Sauer, F., Schmitt, D., Poterszman, A., Egly, J., Kisker., C. (2014) PLoS Biol., 12. doi: 10.1371/journal.pbio.1001954.<br /> # Constantinescu-Aruxandei, D., Petrovic-Stojanovska, B., Penedo, J., White, M., Naismith, J. (2016) Mechanism of DNA loading by the DNA repair helicase XPD, Nucl. Acids Res., 44, 2806-2815.<br /> # Nance MA, Berry SA. (1992) Cockayne syndrome: review of 140 cases, Am J Med Genet 42, 68-84. Review.<br /> # Hengge UR, Emmert S. (2008) Clinical features of xeroderma pigmentosum, Adv Exp Med Biol. 637, 10-8. Review.<br /> # Hashimoto S, Egly JM. (2009) Trichothiodystrophy view from the molecular basis of DNA repair/transcription factor TFIIH, Hum Mol Genet. 18, R224-30. doi: 10.1093/hmg/ddp390. Review.</div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2586307 XPD Helicase (3CRV) 2016-04-10T20:36:58Z

<p>Bashir Noor: </p> <hr /> <div><Structure load='3CRV' size='350' frame='true' align='right' caption='XPD helicase, 3CRV' scene='Insert optional scene name here' /><br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) is a subunit of Transcription Factor II Human (TFIIH).<br /> <br /> == Function ==<br /> XPD helicase is an essential part, or subunit, of the general transcription factor IIH (TFIIH), which is a complex that helps initiate transcription and repair damaged DNA. XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme. Helicases, of which XPD helicase is a type, are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes can act upon the DNA. In the context of DNA repair, these enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to ultraviolet (UV) radiation, adjacent nucleotide bases, often thymines, can react and form bulky dimers, which can block enzymes that work on DNA. To fix this type of damage on single strands of DNA, cells employ a process called nucleotide excision repair (NER). This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove damaged DNA due to UV exposure. <br /> <br /> Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP. <br /> <br /> == Disease ==<br /> Mutations in XPD helicase are associated with three distinct diseases: Cockayne Syndrome (CS), Xeroderma Pigmentosum (XP), and trichothiodystrophy (TTD). The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation.<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer. TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity. Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. <br /> <br /> == Structural highlights ==<br /> <scene name='72/728075/Alpha_helices/4'>Alpha Helices</scene><br /> <br /> <scene name='72/728075/Beta_sheet/3'>Beta Sheets</scene><br /> <br /> <scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene><br /> <br /> <scene name='72/728075/Nucleotide_binding/3'>ATP Binding</scene><br /> <br /> <br /> <br /> <br /> == References ==<br /> <\References></div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2586306 XPD Helicase (3CRV) 2016-04-10T20:35:51Z

<p>Bashir Noor: </p> <hr /> <div><Structure load='3CRV' size='350' frame='true' align='right' caption='XPD helicase, 3CRV' scene='Insert optional scene name here' /><br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) is a subunit of Transcription Factor II Human (TFIIH).<br /> <br /> == Function ==<br /> XPD helicase is an essential part, or subunit, of the general transcription factor IIH (TFIIH), which is a complex that helps initiate transcription and repair damaged DNA. XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme. Helicases, of which XPD helicase is a type, are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes can act upon the DNA. In the context of DNA repair, these enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to ultraviolet (UV) radiation, adjacent nucleotide bases, often thymines, can react and form bulky dimers, which can block enzymes that work on DNA. To fix this type of damage on single strands of DNA, cells employ a process called nucleotide excision repair (NER). This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove damaged DNA due to UV exposure. <br /> <br /> Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP. <br /> <br /> == Disease ==<br /> Mutations in XPD helicase are associated with three distinct diseases: Cockayne Syndrome (CS), Xeroderma Pigmentosum (XP), and trichothiodystrophy (TTD). The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation.<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer. TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity. Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. <br /> <br /> == Structural highlights ==<br /> <scene name='72/728075/Alpha_helices/3'>Alpha Helices</scene><br /> <br /> <scene name='72/728075/Beta_sheet/3'>Beta Sheets</scene><br /> <br /> <scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene><br /> <br /> <scene name='72/728075/Nucleotide_binding/3'>ATP Binding</scene><br /> <br /> <br /> <br /> <br /> == References ==<br /> <\References></div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2586305 XPD Helicase (3CRV) 2016-04-10T20:32:48Z

<p>Bashir Noor: </p> <hr /> <div><Structure load='3CRV' size='350' frame='true' align='right' caption='XPD helicase, 3CRV' scene='Insert optional scene name here' /><br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) is a subunit of Transcription Factor II Human (TFIIH).<br /> <br /> == Function ==<br /> XPD helicase is an essential part, or subunit, of the general transcription factor IIH (TFIIH), which is a complex that helps initiate transcription and repair damaged DNA. XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme. Helicases, of which XPD helicase is a type, are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes can act upon the DNA. In the context of DNA repair, these enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to ultraviolet (UV) radiation, adjacent nucleotide bases, often thymines, can react and form bulky dimers, which can block enzymes that work on DNA. To fix this type of damage on single strands of DNA, cells employ a process called nucleotide excision repair (NER). This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove damaged DNA due to UV exposure. <br /> <br /> Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP. <br /> <br /> == Disease ==<br /> Mutations in XPD helicase are associated with three distinct diseases: Cockayne Syndrome (CS), Xeroderma Pigmentosum (XP), and trichothiodystrophy (TTD). The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation.<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer. TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity. Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. <br /> <br /> == Structural highlights ==<br /> <scene name='72/728075/Alpha_helices/3'>Alpha Helices</scene><br /> <br /> <scene name='72/728075/Beta_sheet/2'>Beta Sheets</scene><br /> <br /> <scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene><br /> <br /> <scene name='72/728075/Nucleotide_binding/3'>ATP Binding</scene><br /> <br /> <br /> <br /> <br /> == References ==<br /> <\References></div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2586301 XPD Helicase (3CRV) 2016-04-10T20:23:12Z

<p>Bashir Noor: </p> <hr /> <div><Structure load='3CRV' size='350' frame='true' align='right' caption='XPD helicase, 3CRV' scene='Insert optional scene name here' /><br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) is a subunit of Transcription Factor II Human (TFIIH).<br /> <br /> == Function ==<br /> XPD helicase is an essential part, or subunit, of the general transcription factor IIH (TFIIH), which is a complex that helps initiate transcription and repair damaged DNA. XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme. Helicases, of which XPD helicase is a type, are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes can act upon the DNA. In the context of DNA repair, these enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to ultraviolet (UV) radiation, adjacent nucleotide bases, often thymines, can react and form bulky dimers, which can block enzymes that work on DNA. To fix this type of damage on single strands of DNA, cells employ a process called nucleotide excision repair (NER). This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove damaged DNA due to UV exposure. <br /> <br /> Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP. <br /> <br /> == Disease ==<br /> Mutations in XPD helicase are associated with three distinct diseases: Cockayne Syndrome (CS), Xeroderma Pigmentosum (XP), and trichothiodystrophy (TTD). The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation.<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer. TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity. Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. <br /> <br /> == Structural highlights ==<br /> <scene name='72/728075/Alpha_helices/3'>Alpha Helices</scene><br /> <br /> <scene name='72/728075/Beta_sheet/2'>Beta Sheets</scene><br /> <br /> <scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene><br /> <br /> <scene name='72/728075/Nucleotide_binding/2'>ATP Binding Region</scene><br /> <br /> <br /> <br /> <br /> == References ==<br /> <\References></div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2586291 XPD Helicase (3CRV) 2016-04-10T20:16:32Z

<p>Bashir Noor: </p> <hr /> <div><Structure load='3CRV' size='350' frame='true' align='right' caption='XPD helicase, 3CRV' scene='Insert optional scene name here' /><br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) is a subunit of Transcription Factor II Human (TFIIH).<br /> <br /> == Function ==<br /> XPD helicase is an essential part, or subunit, of the general transcription factor IIH (TFIIH), which is a complex that helps initiate transcription and repair damaged DNA. XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme. Helicases, of which XPD helicase is a type, are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes can act upon the DNA. In the context of DNA repair, these enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to ultraviolet (UV) radiation, adjacent nucleotide bases, often thymines, can react and form bulky dimers, which can block enzymes that work on DNA. To fix this type of damage on single strands of DNA, cells employ a process called nucleotide excision repair (NER). This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove damaged DNA due to UV exposure. <br /> <br /> Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP. <br /> <br /> <Structure load='3211.pdb' size='350' frame='true' align='right' caption='Ligand Binding' scene='Insert optional scene name here' /><br /> <br /> == Disease ==<br /> Mutations in XPD helicase are associated with three distinct diseases: Cockayne Syndrome (CS), Xeroderma Pigmentosum (XP), and trichothiodystrophy (TTD). The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation.<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer. TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity. Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. <br /> <br /> == Structural highlights ==<br /> <scene name='72/728075/Alpha_helices/3'>Alpha Helices</scene><br /> <br /> <scene name='72/728075/Beta_sheet/2'>Beta Sheets</scene><br /> <br /> <scene name='72/728075/Binding_domain/5'>Helicase-ATP Domain</scene><br /> <br /> <scene name='72/728075/Nucleotide_binding/1'>ATP Binding Region</scene><br /> <br /> <br /> <br /> <br /> == References ==<br /> <\References></div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2586282 XPD Helicase (3CRV) 2016-04-10T20:11:29Z

<p>Bashir Noor: </p> <hr /> <div><Structure load='3CRV' size='350' frame='true' align='right' caption='XPD helicase, 3CRV' scene='Insert optional scene name here' /><br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) is a subunit of Transcription Factor II Human (TFIIH).<br /> <br /> == Function ==<br /> XPD helicase is an essential part, or subunit, of the general transcription factor IIH (TFIIH), which is a complex that helps initiate transcription and repair damaged DNA. XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme. Helicases, of which XPD helicase is a type, are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes can act upon the DNA. In the context of DNA repair, these enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to ultraviolet (UV) radiation, adjacent nucleotide bases, often thymines, can react and form bulky dimers, which can block enzymes that work on DNA. To fix this type of damage on single strands of DNA, cells employ a process called nucleotide excision repair (NER). This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove the damaged DNA. <br /> <br /> Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP. <br /> <br /> == Disease ==<br /> Mutations in XPD helicase are associated with three distinct diseases: Cockayne Syndrome (CS), Xeroderma Pigmentosum (XP), and trichothiodystrophy (TTD). The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation.<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer. TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity. Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. <br /> <br /> == Structural highlights ==<br /> <scene name='72/728075/Alpha_helices/3'>Alpha Helices</scene><br /> <br /> <scene name='72/728075/Beta_sheet/2'>Beta Sheets</scene><br /> <br /> <scene name='72/728075/Binding_domain/3'>Helicase-ATP Domain</scene><br /> <br /> <scene name='72/728075/Nucleotide_binding/1'>ATP Binding Region</scene><br /> <br /> <br /> <br /> <br /> == References ==<br /> <\References></div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2586277 XPD Helicase (3CRV) 2016-04-10T20:07:37Z

<p>Bashir Noor: </p> <hr /> <div><Structure load='3CRV' size='350' frame='true' align='right' caption='XPD helicase, 3CRV' scene='Insert optional scene name here' /><br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) is a subunit of Transcription Factor II Human (TFIIH).<br /> <br /> == Function ==<br /> XPD helicase is an essential part, or subunit, of the general transcription factor IIH (TFIIH), which is a complex that helps initiate transcription and repair damaged DNA. XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme. Helicases, of which XPD helicase is a type, are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes can act upon the DNA. In the context of DNA repair, these enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to ultraviolet (UV) radiation, adjacent nucleotide bases, often thymines, can react and form bulky dimers, which can block enzymes that work on DNA. To fix this type of damage on single strands of DNA, cells employ a process called nucleotide excision repair (NER). This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove the damaged DNA. <br /> <br /> Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP. <br /> <br /> == Disease ==<br /> Mutations in XPD helicase are associated with three distinct diseases: Cockayne Syndrome (CS), Xeroderma Pigmentosum (XP), and trichothiodystrophy (TTD). The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation.<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer. TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity. Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. <br /> <br /> == Structural highlights ==<br /> <scene name='72/728075/Alpha_helices/3'>Alpha Helices</scene><br /> <br /> <scene name='72/728075/Beta_sheet/1'>Beta Sheets</scene><br /> <br /> <scene name='72/728075/Binding_domain/3'>Helicase-ATP Domain</scene><br /> <br /> <scene name='72/728075/Nucleotide_binding/1'>ATP Binding Region</scene><br /> <br /> <br /> <br /> <br /> == References ==<br /> <\References></div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2586268 XPD Helicase (3CRV) 2016-04-10T19:49:45Z

<p>Bashir Noor: </p> <hr /> <div><Structure load='3CRV' size='350' frame='true' align='right' caption='XPD helicase, 3CRV' scene='Insert optional scene name here' /><br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) is a subunit of Transcription Factor II Human (TFIIH).<br /> <br /> == Function ==<br /> XPD helicase is an essential part, or subunit, of the general transcription factor IIH (TFIIH), which is a complex that helps initiate transcription and repair damaged DNA. XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme. Helicases, of which XPD helicase is a type, are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes can act upon the DNA. In the context of DNA repair, these enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to ultraviolet (UV) radiation, adjacent nucleotide bases, often thymines, can react and form bulky dimers, which can block enzymes that work on DNA. To fix this type of damage on single strands of DNA, cells employ a process called nucleotide excision repair (NER). This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove the damaged DNA. <br /> <br /> Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP. <br /> <br /> == Disease ==<br /> Mutations in XPD helicase are associated with three distinct diseases: Cockayne Syndrome (CS), Xeroderma Pigmentosum (XP), and trichothiodystrophy (TTD). The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation.<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer. TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity. Interestingly, only XP has been found to be associated with an increased risk of skin cancer; studies are being conducted to determine why some mutations in XPD helicase result in a higher risk of skin cancer and others do not. <br /> <br /> == Structural highlights ==<br /> <scene name='72/728075/Xpd_helix/1'>Alpha Helices</scene><br /> <br /> <scene name='72/728075/Beta_sheet/1'>Beta Sheet</scene><br /> <br /> <scene name='72/728075/Binding_domain/3'>Helicase-ATP Domain</scene><br /> <br /> <scene name='72/728075/Nucleotide_binding/1'>ATP Binding Region</scene><br /> <br /> <br /> <br /> <br /> == References ==<br /> <\References></div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2586255 XPD Helicase (3CRV) 2016-04-10T19:33:01Z

<p>Bashir Noor: </p> <hr /> <div><Structure load='3CRV' size='350' frame='true' align='right' caption='XPD helicase, 3CRV' scene='Insert optional scene name here' /><br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) is a subunit of Transcription Factor II Human (TFIIH).<br /> <br /> == Function ==<br /> XPD helicase is an essential part, or subunit, of the general transcription factor IIH (TFIIH), which is a complex that helps initiate transcription and repair damaged DNA. XPD helicase helps to stabilize the structure of TFIIH but also plays a functional role in repairing DNA as a helicase enzyme. Helicases, of which XPD helicase is a type, are enzymes that unwind double-stranded DNA into single-stranded DNA so that other enzymes can act upon the DNA. In the context of DNA repair, these enzymes remove the damaged DNA and replace it with the complementary nucleotides based on the other DNA sequence. When DNA is exposed to ultraviolet (UV) radiation, adjacent nucleotide bases, often thymines, can react and form bulky dimers, which can block enzymes that work on DNA. To fix this type of damage on single strands of DNA, cells employ a process called nucleotide excision repair (NER). This is the type of DNA repair that TFIIH, with the help of the XPD helicase subunit, carries out to remove the damaged DNA. <br /> <br /> Breaking the hydrogen bonds that hold the two DNA strands together requires energy, so XPD helicase is dependent on ATP. <br /> <br /> == Disease ==<br /> Mutations in XPD Helicase are associated with three distinct diseases: Cockayne Syndrome (CS), Xeroderma Pigmentosum (XP), and trichothiodystrophy (TTD). The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation.<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer. TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity.<br /> <br /> == Structural highlights ==<br /> <scene name='72/728075/Binding_domain/3'>Helicase-ATP Domain</scene><br /> <br /> <scene name='72/728075/Xpd_helix/1'>Alpha Helices</scene><br /> <br /> <scene name='72/728075/Nucleotide_binding/1'>Nucleotide Binding Region</scene><br /> <br /> <br /> <br /> <br /> == References ==<br /> <\References></div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2586243 XPD Helicase (3CRV) 2016-04-10T19:25:36Z

<p>Bashir Noor: </p> <hr /> <div><Structure load='3CRV' size='350' frame='true' align='right' caption='XPD helicase, 3CRV' scene='Insert optional scene name here' /><br /> == XPD Helicase ==<br /> Xeroderma pigmentosum group D (XPD) is a subunit of Transcription Factor II Human (TFIIH).<br /> <br /> == Function ==<br /> XPD Helicase is essential in nucleotide excision repair (NER), which is a DNA repair mechanism that removes DNA damaged from ultraviolet light (UV). UV light produces bulky DNA adducts, more specifically, thymine dimers, which interfere with base pairing during DNA replication. The resulting gap from the removed DNA is replaced by DNA polymerase. XPD Helicase is also one of the nine subunits of transcription factor II Human (TFIIH). A part of TFIIH, XPD has the responsibility of enzymatically initiating transcription by melting the promoter region, which is an ATP-dependent process. <br /> <br /> == Disease ==<br /> Mutations in XPD Helicase are associated with three distinct diseases: Cockayne Syndrome (CS), Xeroderma Pigmentosum (XP), and trichothiodystrophy (TTD). The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation.<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer. TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity.<br /> <br /> == Structural highlights ==<br /> <scene name='72/728075/Binding_domain/1'>Helicase-ATP Binding Domain</scene><br /> <br /> <scene name='72/728075/Xpd_helix/1'>Alpha Helices</scene><br /> <br /> <scene name='72/728075/Nucleotide_binding/1'>Nucleotide Binding Region</scene><br /> <br /> <br /> <br /> <br /> == References ==<br /> <\References></div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2586236 XPD Helicase (3CRV) 2016-04-10T19:18:14Z

<p>Bashir Noor: </p> <hr /> <div><Structure load='3CRV' size='350' frame='true' align='right' caption='XPD helicase, 3CRV' scene='Insert optional scene name here' /><br /> == Function ==<br /> XPD Helicase is essential in nucleotide excision repair (NER), which is a DNA repair mechanism that removes DNA damaged from ultraviolet light (UV). UV light produces bulky DNA adducts, more specifically, thymine dimers, which interfere with base pairing during DNA replication. The resulting gap from the removed DNA is replaced by DNA polymerase. XPD Helicase is also one of the nine subunits of transcription factor II Human (TFIIH). A part of TFIIH, XPD has the responsibility of enzymatically initiating transcription by melting the promoter region, which is an ATP-dependent process. <br /> <br /> == Disease ==<br /> Mutations in XPD Helicase are associated with three distinct diseases: Cockayne Syndrome (CS), Xeroderma Pigmentosum (XP), and trichothiodystrophy (TTD). The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation.<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer. TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity.<br /> <br /> == Structural highlights ==<br /> <br /> <scene name='72/728075/Xpd_helix/1'>Select Alpha Helices</scene><br /> <scene name='72/728075/Nucleotide_binding/1'>Select Nucleotide Binding Region</scene><br /> <br /> <br /> == References ==<br /> <\References></div>

Bashir Noor https://proteopedia.org/index.php?title=XPD_Helicase_(3CRV)&diff=2586219 XPD Helicase (3CRV) 2016-04-10T19:04:02Z

<p>Bashir Noor: </p> <hr /> <div><Structure load='3CRV' size='350' frame='true' align='right' caption='XPD helicase, 3CRV' scene='Insert optional scene name here' /><br /> <Structure load='123.pdb' size='350' frame='true' align='right' caption='DNA binding' scene='Insert optional scene name here' /><br /> == Function ==<br /> XPD Helicase is essential in nucleotide excision repair (NER), which is a DNA repair mechanism that removes DNA damaged from ultraviolet light (UV). UV light produces bulky DNA adducts, more specifically, thymine dimers, which interfere with base pairing during DNA replication. The resulting gap from the removed DNA is replaced by DNA polymerase. XPD Helicase is also one of the nine subunits of transcription factor II Human (TFIIH). A part of TFIIH, XPD has the responsibility of enzymatically initiating transcription by melting the promoter region, which is an ATP-dependent process. <br /> <br /> == Disease ==<br /> Mutations in XPD Helicase are associated with three distinct diseases: Cockayne Syndrome (CS), Xeroderma Pigmentosum (XP), and trichothiodystrophy (TTD). The common symptom between these diseases is sensitivity to UV light because of defects in the repair system that fixes mutations caused by UV radiation.<br /> CS is characterized by short stature, signs of premature aging, failure to gain weight, impaired development of the nervous system, and photosensitivity. XP is characterized by extreme sensitivity to sunlight and a higher risk of skin cancer. TTD is characterized by sparse and brittle hair, pregnancy-induced high blood pressure, intellectual disabilities, a higher risk of recurrent respiratory infections, and photosensitivity.<br /> <br /> == Structural highlights ==<br /> <scene name='72/728075/Xpd_helix/1'>Select Alpha Helices</scene><br /> <br /> </StructureSection><br /> == References ==<br /> 1. Fan, L., Fuss, J. O., Cheng, Q. J., Arvai, A. S., Hammel, M., Roberts, V. A., Cooper, P. K., and Tainer, J. A. (2008) ''XPD helicase structures and activities: Insights into the cancer and aging phenotypes from XPD mutations.''</div>

Bashir Noor https://proteopedia.org/index.php?title=File:XPD.pdb&diff=2586200 File:XPD.pdb 2016-04-10T18:30:36Z

<p>Bashir Noor: </p> <hr /> <div></div>

Bashir Noor https://proteopedia.org/index.php?title=File:XPD_BoundDNA.pdb&diff=2586196 File:XPD BoundDNA.pdb 2016-04-10T18:25:48Z

<p>Bashir Noor: uploaded a new version of "Image:XPD BoundDNA.pdb"</p> <hr /> <div>== Summary ==<br /> 3CRV bound to DNA<br /> == Licensing ==<br /> {{subst:No license from license selector|Don't know}}</div>

Bashir Noor https://proteopedia.org/index.php?title=File:XPD_DNA.pdb&diff=2586182 File:XPD DNA.pdb 2016-04-10T18:01:05Z

<p>Bashir Noor: XPD bound to DNA</p> <hr /> <div>== Summary ==<br /> XPD bound to DNA<br /> == Licensing ==<br /> {{subst:No license from license selector|Don't know}}</div>

Bashir Noor