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https://proteopedia.org/api.php?action=feedcontributions&feedformat=atom&user=Riley+Hicks Proteopedia - User contributions [en] 2026-09-14T19:52:06Z User contributions MediaWiki 1.43.8 https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1062749 8-Oxoguanine Glycosylase 2010-03-31T06:26:58Z

<p>Riley Hicks: /* Mechanism */</p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction=<br /> 8-oxogunanine glycosylase (hOGG1) is a DNA glycosylase coded from the OGG1 gene in humans; however, many homologs exist in different organisms and this enzyme was originally discovered in yeast<ref name="lu">PMID: 11892789</ref>. It is responsible for removing genotoxic lesions caused by oxidative damage in the presence of reactive oxygen species (ROS)<ref name="lu"/>. Glycosylases, in general, are key enzymes for base excision repair and therefore are essential for maintaining integrity of the genetic material. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases<ref name="lu"/>.<br /> <br /> =Function=<br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> (8-oxoG, GO); this lesion arises from oxidative attack by ROS on G<ref name="lu"/>. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions<ref name="lu"/>. hOGG1 is able to cleave the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site<ref name="lu"/>. It also has the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase<ref name="lu"/>. hOGG1 has greater affinity for GO when it is complementary to C, and hOGG1 also has catalytic activity towards other lesions such as formamidopyrimidines<ref name="lu"/>.<br /> <br /> =Structure=<br /> hOGG1, <scene name='Sandbox_164/Scene_8/1'>a monomer</scene>, belongs to a super family of DNA repair enzymes that share a conserved, two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate<ref name="lu"/>. This motif is necessary for interacting with DNA to recognize and catalyze the substrate <ref name ="Bruner">PMID: 10706276</ref>. As well, OGG1 is associated with two calcium ions that help stabilize the deformed DNA back bone at the site of the extruded lesion<ref name ="Bruner"/>.<br /> <br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>PMID: 11238177</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ by only two atoms at C8 and N7 <ref name="paper"> PMID: 15800616</ref>. <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref name= "GML">PMID: 15642264</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> where residues lining the pocket can directly interact to excise the lesion<ref name="paper"/>. <br /> =====Catalysis=====<br /> To excise GO, Lys 249 acts as a nucleophile attacking the C1' carbon in a SN1 reaction, when GO is inserted into the catalytic pocket<ref name= "GML"/>. Then hOGG1 AP lyase activity uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct that undergoes a series of subsequent transformations resulting in DNA strand exscission on the 3’ side of the lesion<ref name= "GML"/>.<br /> <br /> =Importance of hOGG1=<br /> Oxidative mutations in DNA are heavily implicated in aging and cancer so hOGG1 activity is necessary for many organisms to increase longevity. In fact C:G to T:A tranversions, that can be casued by GO, are very common in tumor suppressor genes and human cancers. GO has even been suggested as an indicator for breast cancer where ROS can accumulate<ref name="lu"/>. Mutations in glycosylase genes, like hOGG1, have also been linked to increased mutation rates<ref name="lu"/>.<br /> <br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1062748 8-Oxoguanine Glycosylase 2010-03-31T06:25:40Z

<p>Riley Hicks: /* Mechanism */</p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction=<br /> 8-oxogunanine glycosylase (hOGG1) is a DNA glycosylase coded from the OGG1 gene in humans; however, many homologs exist in different organisms and this enzyme was originally discovered in yeast<ref name="lu">PMID: 11892789</ref>. It is responsible for removing genotoxic lesions caused by oxidative damage in the presence of reactive oxygen species (ROS)<ref name="lu"/>. Glycosylases, in general, are key enzymes for base excision repair and therefore are essential for maintaining integrity of the genetic material. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases<ref name="lu"/>.<br /> <br /> =Function=<br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> (8-oxoG, GO); this lesion arises from oxidative attack by ROS on G<ref name="lu"/>. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions<ref name="lu"/>. hOGG1 is able to cleave the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site<ref name="lu"/>. It also has the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase<ref name="lu"/>. hOGG1 has greater affinity for GO when it is complementary to C, and hOGG1 also has catalytic activity towards other lesions such as formamidopyrimidines<ref name="lu"/>.<br /> <br /> =Structure=<br /> hOGG1, <scene name='Sandbox_164/Scene_8/1'>a monomer</scene>, belongs to a super family of DNA repair enzymes that share a conserved, two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate<ref name="lu"/>. This motif is necessary for interacting with DNA to recognize and catalyze the substrate <ref name ="Bruner">PMID: 10706276</ref>. As well, OGG1 is associated with two calcium ions that help stabilize the deformed DNA back bone at the site of the extruded lesion<ref name ="Bruner"/>.<br /> <br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>PMID: 11238177</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ by only two at C8 and N7 <ref name="paper"> PMID: 15800616</ref>. <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref name= "GML">PMID: 15642264</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> where residues lining the pocket can directly interact to excise the lesion<ref name="paper"/>. <br /> =====Catalysis=====<br /> To excise GO, Lys 249 acts as a nucleophile attacking the C1' carbon in a SN1 reaction, when GO is inserted into the catalytic pocket<ref name= "GML"/>. Then hOGG1 AP lyase activity uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct that undergoes a series of subsequent transformations resulting in DNA strand exscission on the 3’ side of the lesion<ref name= "GML"/>.<br /> <br /> =Importance of hOGG1=<br /> Oxidative mutations in DNA are heavily implicated in aging and cancer so hOGG1 activity is necessary for many organisms to increase longevity. In fact C:G to T:A tranversions, that can be casued by GO, are very common in tumor suppressor genes and human cancers. GO has even been suggested as an indicator for breast cancer where ROS can accumulate<ref name="lu"/>. Mutations in glycosylase genes, like hOGG1, have also been linked to increased mutation rates<ref name="lu"/>.<br /> <br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1062746 8-Oxoguanine Glycosylase 2010-03-31T06:23:34Z

<p>Riley Hicks: /* Function */</p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction=<br /> 8-oxogunanine glycosylase (hOGG1) is a DNA glycosylase coded from the OGG1 gene in humans; however, many homologs exist in different organisms and this enzyme was originally discovered in yeast<ref name="lu">PMID: 11892789</ref>. It is responsible for removing genotoxic lesions caused by oxidative damage in the presence of reactive oxygen species (ROS)<ref name="lu"/>. Glycosylases, in general, are key enzymes for base excision repair and therefore are essential for maintaining integrity of the genetic material. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases<ref name="lu"/>.<br /> <br /> =Function=<br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> (8-oxoG, GO); this lesion arises from oxidative attack by ROS on G<ref name="lu"/>. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions<ref name="lu"/>. hOGG1 is able to cleave the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site<ref name="lu"/>. It also has the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase<ref name="lu"/>. hOGG1 has greater affinity for GO when it is complementary to C, and hOGG1 also has catalytic activity towards other lesions such as formamidopyrimidines<ref name="lu"/>.<br /> <br /> =Structure=<br /> hOGG1, <scene name='Sandbox_164/Scene_8/1'>a monomer</scene>, belongs to a super family of DNA repair enzymes that share a conserved, two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate<ref name="lu"/>. This motif is necessary for interacting with DNA to recognize and catalyze the substrate <ref name ="Bruner">PMID: 10706276</ref>. As well, OGG1 is associated with two calcium ions that help stabilize the deformed DNA back bone at the site of the extruded lesion<ref name ="Bruner"/>.<br /> <br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>PMID: 11238177</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 <ref name="paper"> PMID: 15800616</ref>. <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref name= "GML">PMID: 15642264</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> where residues lining the pocket can directly interact to excise the lesion<ref name="paper"/>. <br /> =====Catalysis=====<br /> To excise GO, Lys 249 acts as a nucleophile attacking the C1' carbon in a SN1 reaction, when GO is inserted into the catalytic pocket<ref name= "GML"/>. Then hOGG1 AP lyase activity uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct that undergoes a series of subsequent transformations resulting in DNA strand exscission on the 3’ side of the lesion<ref name= "GML"/>.<br /> <br /> =Importance of hOGG1=<br /> Oxidative mutations in DNA are heavily implicated in aging and cancer so hOGG1 activity is necessary for many organisms to increase longevity. In fact C:G to T:A tranversions, that can be casued by GO, are very common in tumor suppressor genes and human cancers. GO has even been suggested as an indicator for breast cancer where ROS can accumulate<ref name="lu"/>. Mutations in glycosylase genes, like hOGG1, have also been linked to increased mutation rates<ref name="lu"/>.<br /> <br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1062745 8-Oxoguanine Glycosylase 2010-03-31T06:21:30Z

<p>Riley Hicks: /* Introduction */</p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction=<br /> 8-oxogunanine glycosylase (hOGG1) is a DNA glycosylase coded from the OGG1 gene in humans; however, many homologs exist in different organisms and this enzyme was originally discovered in yeast<ref name="lu">PMID: 11892789</ref>. It is responsible for removing genotoxic lesions caused by oxidative damage in the presence of reactive oxygen species (ROS)<ref name="lu"/>. Glycosylases, in general, are key enzymes for base excision repair and therefore are essential for maintaining integrity of the genetic material. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases<ref name="lu"/>.<br /> <br /> =Function=<br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> (8-oxoG, GO); this lesion arises from oxidative attack by ROS on G<ref name="lu"/>. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions<ref name="lu"/>. hOGG1 is able to cleave the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site<ref name="lu"/>. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase<ref name="lu"/>. hOGG1 has greater affinity for GO when it is complementary to C, and hOGG1 also has catalytic activity towards other lesions such as formamidopyrimidines<ref name="lu"/>.<br /> <br /> =Structure=<br /> hOGG1, <scene name='Sandbox_164/Scene_8/1'>a monomer</scene>, belongs to a super family of DNA repair enzymes that share a conserved, two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate<ref name="lu"/>. This motif is necessary for interacting with DNA to recognize and catalyze the substrate <ref name ="Bruner">PMID: 10706276</ref>. As well, OGG1 is associated with two calcium ions that help stabilize the deformed DNA back bone at the site of the extruded lesion<ref name ="Bruner"/>.<br /> <br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>PMID: 11238177</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 <ref name="paper"> PMID: 15800616</ref>. <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref name= "GML">PMID: 15642264</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> where residues lining the pocket can directly interact to excise the lesion<ref name="paper"/>. <br /> =====Catalysis=====<br /> To excise GO, Lys 249 acts as a nucleophile attacking the C1' carbon in a SN1 reaction, when GO is inserted into the catalytic pocket<ref name= "GML"/>. Then hOGG1 AP lyase activity uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct that undergoes a series of subsequent transformations resulting in DNA strand exscission on the 3’ side of the lesion<ref name= "GML"/>.<br /> <br /> =Importance of hOGG1=<br /> Oxidative mutations in DNA are heavily implicated in aging and cancer so hOGG1 activity is necessary for many organisms to increase longevity. In fact C:G to T:A tranversions, that can be casued by GO, are very common in tumor suppressor genes and human cancers. GO has even been suggested as an indicator for breast cancer where ROS can accumulate<ref name="lu"/>. Mutations in glycosylase genes, like hOGG1, have also been linked to increased mutation rates<ref name="lu"/>.<br /> <br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1062744 8-Oxoguanine Glycosylase 2010-03-31T06:20:23Z

<p>Riley Hicks: /* Introduction<ref name="lu">PMID: 11892789</ref> */</p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction=<br /> 8-oxogunanine glycosylase (hOGG1) is a DNA glycosylase coded from the OGG1 gene in humans; however, many homologs exist in different organisms and this enzyme was originally discovered in yeast<ref name="lu">PMID: 11892789</ref>. It is responsible for removing genotoxic lesions caused by oxidative damage in the presence of reactive oxygen species (ROS). Glycosylases, in general, are key enzymes for base excision repair and therefore are essential for maintaining integrity of the genetic material. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases.<br /> <br /> =Function=<br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> (8-oxoG, GO); this lesion arises from oxidative attack by ROS on G<ref name="lu"/>. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions<ref name="lu"/>. hOGG1 is able to cleave the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site<ref name="lu"/>. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase<ref name="lu"/>. hOGG1 has greater affinity for GO when it is complementary to C, and hOGG1 also has catalytic activity towards other lesions such as formamidopyrimidines<ref name="lu"/>.<br /> <br /> =Structure=<br /> hOGG1, <scene name='Sandbox_164/Scene_8/1'>a monomer</scene>, belongs to a super family of DNA repair enzymes that share a conserved, two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate<ref name="lu"/>. This motif is necessary for interacting with DNA to recognize and catalyze the substrate <ref name ="Bruner">PMID: 10706276</ref>. As well, OGG1 is associated with two calcium ions that help stabilize the deformed DNA back bone at the site of the extruded lesion<ref name ="Bruner"/>.<br /> <br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>PMID: 11238177</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 <ref name="paper"> PMID: 15800616</ref>. <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref name= "GML">PMID: 15642264</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> where residues lining the pocket can directly interact to excise the lesion<ref name="paper"/>. <br /> =====Catalysis=====<br /> To excise GO, Lys 249 acts as a nucleophile attacking the C1' carbon in a SN1 reaction, when GO is inserted into the catalytic pocket<ref name= "GML"/>. Then hOGG1 AP lyase activity uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct that undergoes a series of subsequent transformations resulting in DNA strand exscission on the 3’ side of the lesion<ref name= "GML"/>.<br /> <br /> =Importance of hOGG1=<br /> Oxidative mutations in DNA are heavily implicated in aging and cancer so hOGG1 activity is necessary for many organisms to increase longevity. In fact C:G to T:A tranversions, that can be casued by GO, are very common in tumor suppressor genes and human cancers. GO has even been suggested as an indicator for breast cancer where ROS can accumulate<ref name="lu"/>. Mutations in glycosylase genes, like hOGG1, have also been linked to increased mutation rates<ref name="lu"/>.<br /> <br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1062743 8-Oxoguanine Glycosylase 2010-03-31T06:19:24Z

<p>Riley Hicks: /* Function <ref name="lu"/> */</p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction<ref name="lu">PMID: 11892789</ref>=<br /> 8-oxogunanine glycosylase (hOGG1) is a DNA glycosylase coded from the OGG1 gene in humans; however, many homologs exist in different organisms and this enzyme was originally discovered in yeast. It is responsible for removing genotoxic lesions caused by oxidative damage in the presence of reactive oxygen species (ROS). Glycosylases, in general, are key enzymes for base excision repair and therefore are essential for maintaining integrity of the genetic material. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases.<br /> <br /> =Function=<br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> (8-oxoG, GO); this lesion arises from oxidative attack by ROS on G<ref name="lu"/>. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions<ref name="lu"/>. hOGG1 is able to cleave the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site<ref name="lu"/>. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase<ref name="lu"/>. hOGG1 has greater affinity for GO when it is complementary to C, and hOGG1 also has catalytic activity towards other lesions such as formamidopyrimidines<ref name="lu"/>.<br /> <br /> =Structure=<br /> hOGG1, <scene name='Sandbox_164/Scene_8/1'>a monomer</scene>, belongs to a super family of DNA repair enzymes that share a conserved, two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate<ref name="lu"/>. This motif is necessary for interacting with DNA to recognize and catalyze the substrate <ref name ="Bruner">PMID: 10706276</ref>. As well, OGG1 is associated with two calcium ions that help stabilize the deformed DNA back bone at the site of the extruded lesion<ref name ="Bruner"/>.<br /> <br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>PMID: 11238177</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 <ref name="paper"> PMID: 15800616</ref>. <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref name= "GML">PMID: 15642264</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> where residues lining the pocket can directly interact to excise the lesion<ref name="paper"/>. <br /> =====Catalysis=====<br /> To excise GO, Lys 249 acts as a nucleophile attacking the C1' carbon in a SN1 reaction, when GO is inserted into the catalytic pocket<ref name= "GML"/>. Then hOGG1 AP lyase activity uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct that undergoes a series of subsequent transformations resulting in DNA strand exscission on the 3’ side of the lesion<ref name= "GML"/>.<br /> <br /> =Importance of hOGG1=<br /> Oxidative mutations in DNA are heavily implicated in aging and cancer so hOGG1 activity is necessary for many organisms to increase longevity. In fact C:G to T:A tranversions, that can be casued by GO, are very common in tumor suppressor genes and human cancers. GO has even been suggested as an indicator for breast cancer where ROS can accumulate<ref name="lu"/>. Mutations in glycosylase genes, like hOGG1, have also been linked to increased mutation rates<ref name="lu"/>.<br /> <br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=Sonic_Hedgehog&diff=1059286 Sonic Hedgehog 2010-03-24T06:17:02Z

<p>Riley Hicks: /* Biosynthesis */</p> <hr /> <div><table style="background-color:#ffffc0" cellpadding="8" width="95%" border="0"><tr><td>Please do NOT make changes to this Sandbox until after April 23, 2010. Sandboxes 151-200 are reserved until then for use by the Chemistry 307 class at UNBC taught by Prof. [[User:Andrea Gorrell|Andrea Gorrell]].</td></tr><br /> <br /> = Sonic Hedgehog =<br /> {{STRUCTURE_1vhh | PDB=1vhh | SCENE=Sandbox_191/Scenedefault/4}}<br /> == Introduction ==<br /> <br /> Sonic hedgehog (Shh) is a member of the Hedgehog (Hh) family of secreted extracellular signaling proteins that serve important roles in regulating both short-range and long-range patterning processes in developing invertebrate and vertebrate tissues <ref> Perrimon N. Hedgehog and beyond. Cell. 1995 Feb 24;80:517-520</ref>. First discovered in ''Drosophila'', where mutations of the ''Hedgehog'' gene produces larvae that are covered in hedgehog-like denticles, Hh proteins are encoded by at least three genes in mammals - ''Sonic, Desert, and Indian hedgehog'' <ref> Echelard Y, Epstein DJ, St-Jacques B, Shen L, Mohler J, Mcmahon JA, Mcmahon AP. Sonic Hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity. Cell. 1993. 75:1417-30</ref>. With the ability to control such fundamental processes as pattern formation in vertebrate limb buds, the formation of motor neurons in the neural tube, and the development and maintenance of tissues and organs, Shh is the most well-studied member of the Hh signaling pathway. Excessive signaling in adult cells has been implicated in the development of several human cancers <ref> Altaba AR, Sanchez P, Dahmane N. GLI and Hedgehog in cancer: tumours, embryos stem cells. Nature Reviews Cancer. 2002 May;2:361-372</ref><ref> di Magliano MP, Hebrok, M. Nature Reviews Cancer. 2003 December;3:903-911</ref>.<br /> <br /> == Biosynthesis ==<br /> <br /> As with all members of the Hh family, Shh biosynthesis begins with an unusual molecular processing event. Following cleavage of its signal peptide, the Shh precursor protein is autocatalytically cleaved into a 19-kDa amino-terminal domain (Shh-N) and a 27-kDa C-terminal domain (Shh-C) <ref> Bumcrot DA, Takada R, McMahon AP. Proteolytic processing yields two secreted forms of sonic hedgehog. 1995 April;15(4);2294-2302</ref>. Spanning residues 24 to 197 in human Shh, Shh-N is responsible for all of the local and long-range signaling activities of Shh. Shh-C possesses an intramolecular transferase activity responsible for covalent attachment of a molecule of cholesterol to the C-terminus of Shh-N. Addition of cholesterol serves to tether Shh-N to the cell membrane, restricting its range of activity to that of local signaling only <ref> Porter JA, Young KE, Beachy PA. Cholesterol modification of hedgehog signalling proteins in animal development. Science. 1996 Oct 11;274:255-259</ref>. Thus, the two domains of Shh are catalytically distinct.<br /> <br /> == Structural Overview ==<br /> <br /> The proposed structure for the native Shh-N protein (1VHH) from Cys 25 to Gly 198 is shown. An α + β sandwich consisting of two <br /> <scene name='Sandbox_191/Scene2/5'> α-helices</scene> and a six-stranded, mixed <scene name='Sandbox_191/Scene3/5'> β-sheet</scene> makes up the core of the structure, along with a two-stranded, antiparallel β-sheet. Although this type of folding arrangement has not yet been seen in other proteins, the presence of a <scene name='Sandbox_191/Scene4/3'>tetrahedrally coordinated zinc ion</scene> in Shh-N bears close structural resemblance to the zinc coordination sites of zinc hydrolases, including thermolysin and carboxypeptidase A. Three amino acid side chains – <scene name='Sandbox_191/Scene4/4'>His 141, Asp 148, and His 183</scene> – are bound to the zinc ion in the crystal structure, along with a single <br /> <scene name='Sandbox_191/Scene4/5'>molecule of water</scene>. Zinc ions that serve a structural role in proteins are normally coordinated by four amino acid side chains, including a cysteine, and are not usually exposed to the surrounding solvent. The presence of a zinc-bound water molecule in Shh-N, by contrast, is indicative of a catalytic function. In zinc hydrolases, a zinc-bound water molecule is key to the protein's enzymatic activity when its proton is removed by a nearby glutamate residue. <scene name='Sandbox_191/Scene4/6'>Glu 177</scene> is believed to serve an analogous role in Shh-N, further supporting a novel, hydrolytic function for this protein. Based on the catalytic mechanisms for thermolysin and carboxypeptidase A, other residues in Shh-N that are believed to be involved in a potential hydrolysis mechanism include <scene name='Sandbox_191/Scene4/7'>His 135, His 181, and Glu 127</scene> <ref>PMID: 7477329</ref>. <br /> <br /> The tetrahedrally coordinated zinc ion of Shh-N, along with the non-coordinating residues believed to assist in hydrolysis, are highly conserved among vertebrate Hh proteins. A potential hydrolytic activity is therefore expected to play an important cellular role. In pursuit of a substrate for Shh-N, it was found that Ala 194 and Lys 195 near the C-terminus of one Shh-N molecule can hydrogen bond with residues in the zinc binding site of a second molecule of Shh-N. This indicates that the protein may be capable of cleaving its own C-terminus, a function that has been suggested to liberate the tethered Shh-N from the cell membrane to facilitate long-range signaling. <br /> <br /> == Signaling Pathway ==<br /> <br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1059285 8-Oxoguanine Glycosylase 2010-03-24T06:12:37Z

<p>Riley Hicks: /* Importance of hOGG1 */</p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction<ref name="lu">PMID: 11892789</ref>=<br /> 8-oxogunanine glycosylase (hOGG1) is a DNA glycosylase coded from the OGG1 gene in humans; however, many homologs exist in different organisms and this enzyme was originally discovered in yeast. It is responsible for removing genotoxic lesions caused by oxidative damage in the presence of reactive oxygen species (ROS). Glycosylases, in general, are key enzymes for base excision repair and therefore are essential for maintaining integrity of the genetic material. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases.<br /> <br /> =Function <ref name="lu"/>=<br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> (8-oxoG, GO); this lesion arises from oxidative attack by ROS on G. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions. hOGG1 is able to cleave the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase. hOGG1 has greater affinity for GO when it is complementary to C, and hOGG1 also has catalytic activity towards other lesions such as formamidopyrimidines.<br /> <br /> =Structure=<br /> hOGG1, <scene name='Sandbox_164/Scene_8/1'>a monomer</scene>, belongs to a super family of DNA repair enzymes that share a conserved, two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate<ref name="lu"/>. This motif is necessary for interacting with DNA to recognize and catalyze the substrate <ref name ="Bruner">PMID: 10706276</ref>. As well, OGG1 is associated with two calcium ions that help stabilize the deformed DNA back bone at the site of the extruded lesion<ref name ="Bruner"/>.<br /> <br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>PMID: 11238177</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 <ref name="paper"> PMID: 15800616</ref>. <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref name= "GML">PMID: 15642264</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> where residues lining the pocket can directly interact to excise the lesion<ref name="paper"/>. <br /> =====Catalysis=====<br /> To excise GO, Lys 249 acts as a nucleophile attacking the C1' carbon in a SN1 reaction, when GO is inserted into the catalytic pocket<ref name= "GML"/>. Then hOGG1 AP lyase activity uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct that undergoes a series of subsequent transformations resulting in DNA strand exscission on the 3’ side of the lesion<ref name= "GML"/>.<br /> <br /> =Importance of hOGG1=<br /> Oxidative mutations in DNA are heavily implicated in aging and cancer so hOGG1 activity is necessary for many organisms to increase longevity. In fact C:G to T:A tranversions, that can be casued by GO, are very common in tumor suppressor genes and human cancers. GO has even been suggested as an indicator for breast cancer where ROS can accumulate<ref name="lu"/>. Mutations in glycosylase genes, like hOGG1, have also been linked to increased mutation rates<ref name="lu"/>.<br /> <br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1059284 8-Oxoguanine Glycosylase 2010-03-24T06:09:59Z

<p>Riley Hicks: /* Catalysis */</p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction<ref name="lu">PMID: 11892789</ref>=<br /> 8-oxogunanine glycosylase (hOGG1) is a DNA glycosylase coded from the OGG1 gene in humans; however, many homologs exist in different organisms and this enzyme was originally discovered in yeast. It is responsible for removing genotoxic lesions caused by oxidative damage in the presence of reactive oxygen species (ROS). Glycosylases, in general, are key enzymes for base excision repair and therefore are essential for maintaining integrity of the genetic material. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases.<br /> <br /> =Function <ref name="lu"/>=<br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> (8-oxoG, GO); this lesion arises from oxidative attack by ROS on G. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions. hOGG1 is able to cleave the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase. hOGG1 has greater affinity for GO when it is complementary to C, and hOGG1 also has catalytic activity towards other lesions such as formamidopyrimidines.<br /> <br /> =Structure=<br /> hOGG1, <scene name='Sandbox_164/Scene_8/1'>a monomer</scene>, belongs to a super family of DNA repair enzymes that share a conserved, two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate<ref name="lu"/>. This motif is necessary for interacting with DNA to recognize and catalyze the substrate <ref name ="Bruner">PMID: 10706276</ref>. As well, OGG1 is associated with two calcium ions that help stabilize the deformed DNA back bone at the site of the extruded lesion<ref name ="Bruner"/>.<br /> <br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>PMID: 11238177</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 <ref name="paper"> PMID: 15800616</ref>. <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref name= "GML">PMID: 15642264</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> where residues lining the pocket can directly interact to excise the lesion<ref name="paper"/>. <br /> =====Catalysis=====<br /> To excise GO, Lys 249 acts as a nucleophile attacking the C1' carbon in a SN1 reaction, when GO is inserted into the catalytic pocket<ref name= "GML"/>. Then hOGG1 AP lyase activity uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct that undergoes a series of subsequent transformations resulting in DNA strand exscission on the 3’ side of the lesion<ref name= "GML"/>.<br /> <br /> =Importance of hOGG1=<br /> Oxidative mutations in DNA are heavily implicated in aging and cancer so it is important that hOGG1 remove certain lesions to increase longevity. In fact C:G to T:A tranversions, that can be casued by GO, are very common in tumor suppressor genes and human cancers. GO has even been suggested as an indicator for breast cancer where ROS can accumulate<ref name="lu"/>. Mutations in glycosylase genes, like hOGG1, have also been linked to increased mutation rates<ref name="lu"/>.<br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1059283 8-Oxoguanine Glycosylase 2010-03-24T06:07:17Z

<p>Riley Hicks: /* Structure */</p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction<ref name="lu">PMID: 11892789</ref>=<br /> 8-oxogunanine glycosylase (hOGG1) is a DNA glycosylase coded from the OGG1 gene in humans; however, many homologs exist in different organisms and this enzyme was originally discovered in yeast. It is responsible for removing genotoxic lesions caused by oxidative damage in the presence of reactive oxygen species (ROS). Glycosylases, in general, are key enzymes for base excision repair and therefore are essential for maintaining integrity of the genetic material. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases.<br /> <br /> =Function <ref name="lu"/>=<br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> (8-oxoG, GO); this lesion arises from oxidative attack by ROS on G. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions. hOGG1 is able to cleave the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase. hOGG1 has greater affinity for GO when it is complementary to C, and hOGG1 also has catalytic activity towards other lesions such as formamidopyrimidines.<br /> <br /> =Structure=<br /> hOGG1, <scene name='Sandbox_164/Scene_8/1'>a monomer</scene>, belongs to a super family of DNA repair enzymes that share a conserved, two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate<ref name="lu"/>. This motif is necessary for interacting with DNA to recognize and catalyze the substrate <ref name ="Bruner">PMID: 10706276</ref>. As well, OGG1 is associated with two calcium ions that help stabilize the deformed DNA back bone at the site of the extruded lesion<ref name ="Bruner"/>.<br /> <br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>PMID: 11238177</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 <ref name="paper"> PMID: 15800616</ref>. <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref name= "GML">PMID: 15642264</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> where residues lining the pocket can directly interact to excise the lesion<ref name="paper"/>. <br /> =====Catalysis=====<br /> To excise GO, Lys 249 acts as a nucleophile attacking the C1' carbon in a SN1 reaction, when GO is inserted into the catalytic pocket<ref name= "GML"/>. Then hOGG1 AP lyase uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct, which undergoes a series of subsequent transformation resulting in DNA strand exscission on the 3’ side of the lesion<ref name= "GML"/>.<br /> =Importance of hOGG1=<br /> Oxidative mutations in DNA are heavily implicated in aging and cancer so it is important that hOGG1 remove certain lesions to increase longevity. In fact C:G to T:A tranversions, that can be casued by GO, are very common in tumor suppressor genes and human cancers. GO has even been suggested as an indicator for breast cancer where ROS can accumulate<ref name="lu"/>. Mutations in glycosylase genes, like hOGG1, have also been linked to increased mutation rates<ref name="lu"/>.<br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1059282 8-Oxoguanine Glycosylase 2010-03-24T06:06:17Z

<p>Riley Hicks: /* Function <ref name="lu"/> */</p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction<ref name="lu">PMID: 11892789</ref>=<br /> 8-oxogunanine glycosylase (hOGG1) is a DNA glycosylase coded from the OGG1 gene in humans; however, many homologs exist in different organisms and this enzyme was originally discovered in yeast. It is responsible for removing genotoxic lesions caused by oxidative damage in the presence of reactive oxygen species (ROS). Glycosylases, in general, are key enzymes for base excision repair and therefore are essential for maintaining integrity of the genetic material. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases.<br /> <br /> =Function <ref name="lu"/>=<br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> (8-oxoG, GO); this lesion arises from oxidative attack by ROS on G. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions. hOGG1 is able to cleave the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase. hOGG1 has greater affinity for GO when it is complementary to C, and hOGG1 also has catalytic activity towards other lesions such as formamidopyrimidines.<br /> <br /> =Structure=<br /> hOGG1, <scene name='Sandbox_164/Scene_8/1'>a monomer</scene>, belongs to a super family of DNA repair enzymes that share a conserved two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate<ref name="lu"/>. This motif is necessary for interacting with DNA to recognize and catalyze the substrate <ref name ="Bruner">PMID: 10706276</ref>. As well, OGG1 is associated with two calcium ions that help stabilize the deformed DNA back bone at the site of the extruded lesion<ref name ="Bruner"/>.<br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>PMID: 11238177</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 <ref name="paper"> PMID: 15800616</ref>. <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref name= "GML">PMID: 15642264</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> where residues lining the pocket can directly interact to excise the lesion<ref name="paper"/>. <br /> =====Catalysis=====<br /> To excise GO, Lys 249 acts as a nucleophile attacking the C1' carbon in a SN1 reaction, when GO is inserted into the catalytic pocket<ref name= "GML"/>. Then hOGG1 AP lyase uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct, which undergoes a series of subsequent transformation resulting in DNA strand exscission on the 3’ side of the lesion<ref name= "GML"/>.<br /> =Importance of hOGG1=<br /> Oxidative mutations in DNA are heavily implicated in aging and cancer so it is important that hOGG1 remove certain lesions to increase longevity. In fact C:G to T:A tranversions, that can be casued by GO, are very common in tumor suppressor genes and human cancers. GO has even been suggested as an indicator for breast cancer where ROS can accumulate<ref name="lu"/>. Mutations in glycosylase genes, like hOGG1, have also been linked to increased mutation rates<ref name="lu"/>.<br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1059281 8-Oxoguanine Glycosylase 2010-03-24T06:05:24Z

<p>Riley Hicks: /* Function <ref name="lu"/> */</p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction<ref name="lu">PMID: 11892789</ref>=<br /> 8-oxogunanine glycosylase (hOGG1) is a DNA glycosylase coded from the OGG1 gene in humans; however, many homologs exist in different organisms and this enzyme was originally discovered in yeast. It is responsible for removing genotoxic lesions caused by oxidative damage in the presence of reactive oxygen species (ROS). Glycosylases, in general, are key enzymes for base excision repair and therefore are essential for maintaining integrity of the genetic material. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases.<br /> <br /> =Function <ref name="lu"/>=<br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> (8-oxoG, GO); this lesion is caused by oxidative attack by ROS on G. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions. hOGG1 is able to cleave the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase. hOGG1 has greater affinity for GO when it is complementary to C, and hOGG1 also has catalytic activity towards other lesions such as formamidopyrimidines.<br /> <br /> =Structure=<br /> hOGG1, <scene name='Sandbox_164/Scene_8/1'>a monomer</scene>, belongs to a super family of DNA repair enzymes that share a conserved two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate<ref name="lu"/>. This motif is necessary for interacting with DNA to recognize and catalyze the substrate <ref name ="Bruner">PMID: 10706276</ref>. As well, OGG1 is associated with two calcium ions that help stabilize the deformed DNA back bone at the site of the extruded lesion<ref name ="Bruner"/>.<br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>PMID: 11238177</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 <ref name="paper"> PMID: 15800616</ref>. <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref name= "GML">PMID: 15642264</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> where residues lining the pocket can directly interact to excise the lesion<ref name="paper"/>. <br /> =====Catalysis=====<br /> To excise GO, Lys 249 acts as a nucleophile attacking the C1' carbon in a SN1 reaction, when GO is inserted into the catalytic pocket<ref name= "GML"/>. Then hOGG1 AP lyase uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct, which undergoes a series of subsequent transformation resulting in DNA strand exscission on the 3’ side of the lesion<ref name= "GML"/>.<br /> =Importance of hOGG1=<br /> Oxidative mutations in DNA are heavily implicated in aging and cancer so it is important that hOGG1 remove certain lesions to increase longevity. In fact C:G to T:A tranversions, that can be casued by GO, are very common in tumor suppressor genes and human cancers. GO has even been suggested as an indicator for breast cancer where ROS can accumulate<ref name="lu"/>. Mutations in glycosylase genes, like hOGG1, have also been linked to increased mutation rates<ref name="lu"/>.<br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1059280 8-Oxoguanine Glycosylase 2010-03-24T06:03:47Z

<p>Riley Hicks: /* Introduction<ref name="lu">PMID: 11892789</ref> */</p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction<ref name="lu">PMID: 11892789</ref>=<br /> 8-oxogunanine glycosylase (hOGG1) is a DNA glycosylase coded from the OGG1 gene in humans; however, many homologs exist in different organisms and this enzyme was originally discovered in yeast. It is responsible for removing genotoxic lesions caused by oxidative damage in the presence of reactive oxygen species (ROS). Glycosylases, in general, are key enzymes for base excision repair and therefore are essential for maintaining integrity of the genetic material. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases.<br /> <br /> =Function <ref name="lu"/>=<br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> (8-oxoG, GO); this lesion is caused by oxidative attack by ROS on G. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions. hOGG1 is able to cleave the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase. hOGG1 has greater affinity for GO when is complementary to C, and also has catalytic activity towards other lesions such as formamidopyrimidines. <br /> =Structure=<br /> hOGG1, <scene name='Sandbox_164/Scene_8/1'>a monomer</scene>, belongs to a super family of DNA repair enzymes that share a conserved two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate<ref name="lu"/>. This motif is necessary for interacting with DNA to recognize and catalyze the substrate <ref name ="Bruner">PMID: 10706276</ref>. As well, OGG1 is associated with two calcium ions that help stabilize the deformed DNA back bone at the site of the extruded lesion<ref name ="Bruner"/>.<br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>PMID: 11238177</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 <ref name="paper"> PMID: 15800616</ref>. <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref name= "GML">PMID: 15642264</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> where residues lining the pocket can directly interact to excise the lesion<ref name="paper"/>. <br /> =====Catalysis=====<br /> To excise GO, Lys 249 acts as a nucleophile attacking the C1' carbon in a SN1 reaction, when GO is inserted into the catalytic pocket<ref name= "GML"/>. Then hOGG1 AP lyase uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct, which undergoes a series of subsequent transformation resulting in DNA strand exscission on the 3’ side of the lesion<ref name= "GML"/>.<br /> =Importance of hOGG1=<br /> Oxidative mutations in DNA are heavily implicated in aging and cancer so it is important that hOGG1 remove certain lesions to increase longevity. In fact C:G to T:A tranversions, that can be casued by GO, are very common in tumor suppressor genes and human cancers. GO has even been suggested as an indicator for breast cancer where ROS can accumulate<ref name="lu"/>. Mutations in glycosylase genes, like hOGG1, have also been linked to increased mutation rates<ref name="lu"/>.<br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1059279 8-Oxoguanine Glycosylase 2010-03-24T06:03:12Z

<p>Riley Hicks: /* Introduction<ref name="lu">PMID: 11892789</ref> */</p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction<ref name="lu">PMID: 11892789</ref>=<br /> 8-oxogunanine glycosylase (hOGG1) is a DNA glycosylase, coded from the OGG1 gene in humans; however, many homologs exist in different organisms and this enzyme was originally discovered in yeast. It is responsible for removing genotoxic lesions caused by oxidative damage in the presence of reactive oxygen species (ROS). Glycosylases, in general, are key enzymes for base excision repair and therefore are essential for maintaining integrity of the genetic material. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases.<br /> <br /> =Function <ref name="lu"/>=<br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> (8-oxoG, GO); this lesion is caused by oxidative attack by ROS on G. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions. hOGG1 is able to cleave the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase. hOGG1 has greater affinity for GO when is complementary to C, and also has catalytic activity towards other lesions such as formamidopyrimidines. <br /> =Structure=<br /> hOGG1, <scene name='Sandbox_164/Scene_8/1'>a monomer</scene>, belongs to a super family of DNA repair enzymes that share a conserved two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate<ref name="lu"/>. This motif is necessary for interacting with DNA to recognize and catalyze the substrate <ref name ="Bruner">PMID: 10706276</ref>. As well, OGG1 is associated with two calcium ions that help stabilize the deformed DNA back bone at the site of the extruded lesion<ref name ="Bruner"/>.<br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>PMID: 11238177</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 <ref name="paper"> PMID: 15800616</ref>. <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref name= "GML">PMID: 15642264</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> where residues lining the pocket can directly interact to excise the lesion<ref name="paper"/>. <br /> =====Catalysis=====<br /> To excise GO, Lys 249 acts as a nucleophile attacking the C1' carbon in a SN1 reaction, when GO is inserted into the catalytic pocket<ref name= "GML"/>. Then hOGG1 AP lyase uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct, which undergoes a series of subsequent transformation resulting in DNA strand exscission on the 3’ side of the lesion<ref name= "GML"/>.<br /> =Importance of hOGG1=<br /> Oxidative mutations in DNA are heavily implicated in aging and cancer so it is important that hOGG1 remove certain lesions to increase longevity. In fact C:G to T:A tranversions, that can be casued by GO, are very common in tumor suppressor genes and human cancers. GO has even been suggested as an indicator for breast cancer where ROS can accumulate<ref name="lu"/>. Mutations in glycosylase genes, like hOGG1, have also been linked to increased mutation rates<ref name="lu"/>.<br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1058341 8-Oxoguanine Glycosylase 2010-03-20T19:14:37Z

<p>Riley Hicks: </p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction<ref name="lu">PMID: 11892789</ref>=<br /> 8-Oxogunanine glycosylase (hOGG1) is a DNA glycosylase, coded from the OGG1 gene in humans; however, many homologs exist in different organisms and this enzyme was originally discovered in yeast. It is responsible for removing genotoxic lesions caused by oxidative damage in the presence of reactive oxygen species (ROS). Glycosylases, in general, are key enzymes for base excision repair and therefore maintaining integrity of DNA across the evolutionary spectrum. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases. <br /> =Function <ref name="lu"/>=<br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> (8-oxoG, GO); this lesion is caused by oxidative attack by ROS on G. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions. hOGG1 is able to cleave the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase. hOGG1 has greater affinity for GO when is complementary to C, and also has catalytic activity towards other lesions such as formamidopyrimidines. <br /> =Structure=<br /> hOGG1, <scene name='Sandbox_164/Scene_8/1'>a monomer</scene>, belongs to a super family of DNA repair enzymes that share a conserved two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate<ref name="lu"/>. This motif is necessary for interacting with DNA to recognize and catalyze the substrate <ref name ="Bruner">PMID: 10706276</ref>. As well, OGG1 is associated with two calcium ions that help stabilize the deformed DNA back bone at the site of the extruded lesion<ref name ="Bruner"/>.<br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>PMID: 11238177</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 <ref name="paper"> PMID: 15800616</ref>. <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref name= "GML">PMID: 15642264</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> where residues lining the pocket can directly interact to excise the lesion<ref name="paper"/>. <br /> =====Catalysis=====<br /> To excise GO, Lys 249 acts as a nucleophile attacking the C1' carbon in a SN1 reaction, when GO is inserted into the catalytic pocket<ref name= "GML"/>. Then hOGG1 AP lyase uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct, which undergoes a series of subsequent transformation resulting in DNA strand exscission on the 3’ side of the lesion<ref name= "GML"/>.<br /> =Importance of hOGG1=<br /> Oxidative mutations in DNA are heavily implicated in aging and cancer so it is important that hOGG1 remove certain lesions to increase longevity. In fact C:G to T:A tranversions, that can be casued by GO, are very common in tumor suppressor genes and human cancers. GO has even been suggested as an indicator for breast cancer where ROS can accumulate<ref name="lu"/>. Mutations in glycosylase genes, like hOGG1, have also been linked to increased mutation rates<ref name="lu"/>.<br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1058336 8-Oxoguanine Glycosylase 2010-03-20T19:10:39Z

<p>Riley Hicks: </p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction<ref name="lu">PMID: 11892789</ref>=<br /> 8-Oxogunanine glycosylase (hOGG1) is a DNA glycosylase, coded from the OGG1 gene in humans; however, many homologs exist in different organisms and this enzyme was originally discovered in yeast. It is responsible for removing genotoxic lesions caused by oxidative damage in the presence of reactive oxygen species (ROS). Glycosylases, in general, are key enzymes for base excision repair and therefore maintaining integrity of DNA across the evolutionary spectrum. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases. <br /> =Function <ref name="lu"/>=<br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> (8-oxoG, GO); this lesion is caused by oxidative attack by ROS on G. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions. hOGG1 is able to cleave the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase. hOGG1 has greater affinity for GO when is complementary to C, and also has catalytic activity towards other lesions such as formamidopyrimidines. <br /> =Structure=<br /> hOGG1,<scene name='Sandbox_164/Scene_8/1'>a monomer</scene>, belongs to a super family of DNA repair enzymes that share a conserved two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate<ref name="lu"/>. This motif is necessary for interacting with DNA to recognize and catalyze the substrate <ref name ="Bruner">PMID: 10706276</ref>. As well, OGG1 is associated with two calcium ions that help stabilize the deformed DNA back bone at the site of the extruded lesion<ref name ="Bruner"/>.<br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>PMID: 11238177</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 <ref name="paper"> PMID: 15800616</ref>. <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref name= "GML">PMID: 15642264</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> where residues lining the pocket can directly interact to excise the lesion<ref name="paper"/>. <br /> =====Catalysis=====<br /> To excise GO, Lys 249 acts as a nucleophile attacking the C1' carbon in a SN1 reaction, when GO is inserted into the catalytic pocket<ref name= "GML"/>. Then hOGG1 AP lyase uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct, which undergoes a series of subsequent transformation resulting in DNA strand exscission on the 3’ side of the lesion<ref name= "GML"/>.<br /> =Importance of hOGG1=<br /> Oxidative mutations in DNA are heavily implicated in aging and cancer so it is important that hOGG1 remove certain lesions to increase longevity. In fact C:G to T:A tranversions, that can be casued by GO, are very common in tumor suppressor genes and human cancers. GO has even been suggested as an indicator for breast cancer where ROS can accumulate<ref name="lu"/>. Mutations in glycosylase genes, like hOGG1, have also been linked to increased mutation rates<ref name="lu"/>.<br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1058335 8-Oxoguanine Glycosylase 2010-03-20T19:09:45Z

<p>Riley Hicks: </p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction<ref name="lu">PMID: 11892789</ref>=<br /> 8-Oxogunanine glycosylase (hOGG1) is a DNA glycosylase, coded from the OGG1 gene in humans; however, many homologs exist in different organisms and this enzyme was originally discovered in yeast. It is responsible for removing genotoxic lesions caused by oxidative damage in the presence of reactive oxygen species (ROS). Glycosylases, in general, are key enzymes for base excision repair and therefore maintaining integrity of DNA across the evolutionary spectrum. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases. <br /> =Function <ref name="lu"/>=<br /> hOGG1, a monomer, repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> (8-oxoG, GO); this lesion is caused by oxidative attack by ROS on G. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions. hOGG1 is able to cleave the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase. hOGG1 has greater affinity for GO when is complementary to C, and also has catalytic activity towards other lesions such as formamidopyrimidines. <br /> =Structure=<br /> hOGG1,<scene name='Sandbox_164/Scene_8/1'>a monomer</scene>, belongs to a super family of DNA repair enzymes that share a conserved two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate<ref name="lu"/>. This motif is necessary for interacting with DNA to recognize and catalyze the substrate <ref name ="Bruner">PMID: 10706276</ref>. As well, OGG1 is associated with two calcium ions that help stabilize the deformed DNA back bone at the site of the extruded lesion<ref name ="Bruner"/>.<br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>PMID: 11238177</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 <ref name="paper"> PMID: 15800616</ref>. <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref name= "GML">PMID: 15642264</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> where residues lining the pocket can directly interact to excise the lesion<ref name="paper"/>. <br /> =====Catalysis=====<br /> To excise GO, Lys 249 acts as a nucleophile attacking the C1' carbon in a SN1 reaction, when GO is inserted into the catalytic pocket<ref name= "GML"/>. Then hOGG1 AP lyase uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct, which undergoes a series of subsequent transformation resulting in DNA strand exscission on the 3’ side of the lesion<ref name= "GML"/>.<br /> =Importance of hOGG1=<br /> Oxidative mutations in DNA are heavily implicated in aging and cancer so it is important that hOGG1 remove certain lesions to increase longevity. In fact C:G to T:A tranversions, that can be casued by GO, are very common in tumor suppressor genes and human cancers. GO has even been suggested as an indicator for breast cancer where ROS can accumulate<ref name="lu"/>. Mutations in glycosylase genes, like hOGG1, have also been linked to increased mutation rates<ref name="lu"/>.<br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1058129 8-Oxoguanine Glycosylase 2010-03-19T06:20:41Z

<p>Riley Hicks: </p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction<ref name="lu">PMID: 11892789</ref>=<br /> 8-Oxogunanine glycosylase (hOGG1) is a DNA glycosylase, coded from the OGG1 gene in humans; however, many homologs exist in different organisms and this enzyme was originally discovered in yeast. It is responsible for removing genotoxic lesions caused by oxidative damage in the presence of reactive oxygen species (ROS). Glycosylases, in general, are key enzymes for base excision repair and therefore maintaining integrity of DNA across the evolutionary spectrum. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases. <br /> =Function <ref name="lu"/>=<br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> (8-oxoG, GO); this lesion is caused by oxidative attack by ROS on G. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions. hOGG1 is able to cleave the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase. hOGG1 has greater affinity for GO when is complementary to C, and also has catalytic activity towards other lesions such as formamidopyrimidines. <br /> =Structure=<br /> hOGG1 belongs to a super family of DNA repair enzymes that share a conserved two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate<ref name="lu"/>. This motif is necessary for interacting with DNA to recognize and catalyze the substrate <ref name ="Bruner">PMID: 10706276</ref>. As well, OGG1 is associated with two calcium ions that help stabilize the deformed DNA back bone at the site of the extruded lesion<ref name ="Bruner"/>.<br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>PMID: 11238177</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 <ref name="paper"> PMID: 15800616</ref>. <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref name= "GML">PMID: 15642264</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> where residues lining the pocket can directly interact to excise the lesion<ref name="paper"/>. <br /> =====Catalysis=====<br /> To excise GO, Lys 249 acts as a nucleophile attacking the C1' carbon in a SN1 reaction, when GO is inserted into the catalytic pocket<ref name= "GML"/>. Then hOGG1 AP lyase uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct, which undergoes a series of subsequent transformation resulting in DNA strand exscission on the 3’ side of the lesion<ref name= "GML"/>.<br /> =Importance of hOGG1=<br /> Oxidative mutations in DNA are heavily implicated in aging and cancer so it is important that hOGG1 remove certain lesions to increase longevity. In fact C:G to T:A tranversions, that can be casued by GO, are very common in tumor suppressor genes and human cancers. GO has even been suggested as an indicator for breast cancer where ROS can accumulate<ref name="lu"/>. Mutations in glycosylase genes, like hOGG1, have also been linked to increased mutation rates<ref name="lu"/>.<br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1058128 8-Oxoguanine Glycosylase 2010-03-19T06:19:31Z

<p>Riley Hicks: </p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction<ref name="lu">PMID: 11892789</ref>=<br /> 8-Oxogunanine glycosylase (hOGG1) is a DNA glycosylase, coded from the OGG1 gene in humans; however, many homologs exist in different organisms and this enzyme was originally discovered in yeast. It is responsible for removing genotoxic lesions caused by oxidative damage in the presence of reactive oxygen species (ROS). Glycosylases, in general, are key enzymes for base excision repair and therefore maintaining integrity of DNA across the evolutionary spectrum. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases. <br /> =Function <ref name="lu"/>=<br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> (8-oxoG, GO); this lesion is caused by oxidative attack by ROS on G. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions. hOGG1 is able to cleave the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase. hOGG1 has greater affinity for GO when is complementary to C, and also has catalytic activity towards other lesions such as formamidopyrimidines. <br /> =Structure=<br /> hOGG1 belongs to a super family of DNA repair enzymes that share a conserved two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate<ref name="lu"/>. This motif is necessary for interacting with DNA to recognize and catalyze the substrate <ref name ="Bruner">PMID: 10706276</ref>. As well, OGG1 is associated with two calcium ions that help stabilize the deformed DNA back bone at the site of the extruded lesion<ref name ="Bruner"/>.<br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>PMID: 11238177</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 <ref name="paper"> PMID: 15800616</ref>. <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref name= "GML">PMID: 15642264</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> where residues lining the pocket can directly interact to excise the lesion<ref name="paper"/>. <br /> =====Catalysis=====<br /> To excise GO, Lys 249 acts as a nucleophile attacking the C1' carbon in a SN1 reaction, when GO is inserted into the catalytic pocket<ref name= "GML"/>. Then hOGG1 AP lyase uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct, which undergoes a series of subsequent transformation resulting in DNA strand exscission on the 3’ side of the lesion<ref name= "GML"/>.<br /> =Importance of hOGG1=<br /> Oxidative mutations in DNA are heavily implicated in aging and cancer so it is important that hOGG1 remove certain lesions to increase longevity. In fact C:G T:A tranversions, that can be casued by GO, are very common in tumor suppressor genes and human cancers. GO has even been suggested as an indicator for breast cancer where ROS can accumulate<ref name="lu"/>. Mutations in glycosylase genes, like hOGG1, have also been linked to increased mutation rates<ref name="lu"/>.<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1058127 8-Oxoguanine Glycosylase 2010-03-19T06:16:44Z

<p>Riley Hicks: </p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction<ref name="lu">PMID: 11892789</ref>=<br /> 8-Oxogunanine glycosylase (hOGG1) is a DNA glycosylase, coded from the OGG1 gene in humans; however, many homologs exist in different organisms and this enzyme was originally discovered in yeast. It is responsible for removing genotoxic lesions caused by oxidative damage in the presence of reactive oxygen species (ROS). Glycosylases, in general, are key enzymes for base excision repair and therefore maintaining integrity of DNA across the evolutionary spectrum. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases. <br /> =Function <ref name="lu"/>=<br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> (8-oxoG, GO); this lesion is caused by oxidative attack by ROS on G. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions. hOGG1 is able to cleave the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase. hOGG1 has greater affinity for GO when is complementary to C, and also has catalytic activity towards other lesions such as formamidopyrimidines. <br /> =Structure=<br /> hOGG1 belongs to a super family of DNA repair enzymes that share a conserved two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate<ref name="lu"/>. This motif is necessary for interacting with DNA to recognize and catalyze the substrate <ref name ="Bruner">PMID: 10706276</ref>. As well, OGG1 is associated with two calcium ions that help stabilize the deformed DNA back bone at the site of the extruded lesion<ref name ="Bruner"/>.<br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>PMID: 11238177</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 <ref name="paper"> PMID: 15800616</ref>. <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref name= "GML">PMID: 15642264</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> where residues lining the pocket can directly interact to excise the lesion<ref name="paper"/>. <br /> =====Catalysis=====<br /> To excise GO, Lys 249 acts as a nucleophile attacking the C1' carbon in a SN1 reaction, when GO is inserted into the catalytic pocket<ref name= "GML"/>. Then hOGG1 AP lyase uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct, which undergoes a series of subsequent transformation resulting in DNA strand exscission on the 3’ side of the lesion<ref name= "GML"/>.<br /> =Importance of hOGG1=<br /> Oxidative mutations in DNA are heavily implicated in aging and cancer so it is important that hOGG1 remove certain lesions. In fact C:G T:A tranversions, that can be casued by GO, are very common in tumor suppressor genes and human cancers. GO has even been suggested as an indicator for breast cancer where ROS can accumulate<ref name="lu"/>. Mutations in glycosylase genes, like hOGG1, lead to increased mutation rates that<ref name="lu"/>.hOGG1 and other glycosylases are need to repair DNA to increase longevity.<br /> =References=<br /> <br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1058124 8-Oxoguanine Glycosylase 2010-03-19T06:14:13Z

<p>Riley Hicks: </p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction<ref name="lu">PMID: 11892789</ref>=<br /> 8-Oxogunanine glycosylase (hOGG1) is a DNA glycosylase, coded from the OGG1 gene in humans; however, many homologs exist in different organisms and this enzyme was originally discovered in yeast. It is responsible for removing genotoxic lesions caused by oxidative damage in the presence of reactive oxygen species (ROS). Glycosylases, in general, are key enzymes for base excision repair and therefore maintaining integrity of DNA across the evolutionary spectrum. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases. <br /> =Function <ref name="lu"/>=<br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> (8-oxoG, GO); this lesion is caused by oxidative attack by ROS on G. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions. hOGG1 is able to cleave the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase. hOGG1 has greater affinity for GO when is complementary to C, and also has catalytic activity towards other lesions such as formamidopyrimidines. <br /> =Structure=<br /> hOGG1 belongs to a super family of DNA repair enzymes that share a conserved two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate<ref name="lu"/>. This motif is necessary for interacting with DNA to recognize and catalyze the substrate <ref name ="Bruner">PMID: 10706276</ref>. As well, OGG1 is associated with two calcium ions that help stabilize the deformed DNA back bone at the site of the extruded lesion<ref name ="Bruner"/>.<br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>PMID: 11238177</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 <ref name="paper"> PMID: 15800616</ref>. <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref name= "GML">PMID: 15642264</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> where residues lining the pocket can directly interact to excise the lesion<ref name="paper"/>. <br /> =====Catalysis=====<br /> To excise GO, Lys 249 acts as a nucleophile attacking the C1' carbon in a SN1 reaction, when GO is inserted into the catalytic pocket<ref name= "GML"/>. Then hOGG1 AP lyase uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct, which undergoes a series of subsequent transformation resulting in DNA strand exscission on the 3’ side of the lesion<ref name= "GML"/>.<br /> =Importance of hOGG1=<br /> hOGG1 is an important enzyme to remove lesions in DNA. Oxidative mutations in DNA are heavily implicated in aging and cancer. In fact C:G T:A tranversions are very common in tumor suppressor genes and human cancers and 8-OxoG has been suggested as an indicator for breast cancer where ROS can accumulate<ref name="lu"/>. Mutations in glycosylase genes, like hOGG1, lead to increased mutation rates <ref name="lu"/>.hOGG1 and other glycosylases are need to repair DNA to increase longevity.<br /> =References=<br /> <br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1058118 8-Oxoguanine Glycosylase 2010-03-19T05:49:53Z

<p>Riley Hicks: </p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction<ref name="lu">PMID: 11892789</ref>=<br /> 8-Oxogunanine glycosylase (hOGG1) is a DNA glycosylase, coded from the OGG1 gene in humans; however, many homologs exist in different organisms and this enzyme was originally discovered in yeast. It is responsible for removing genotoxic lesions caused by oxidative damage in the presence of reactive oxygen species (ROS). Glycosylases, in general, are key enzymes for base excision repair and therefore maintaining integrity of DNA across the evolutionary spectrum. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases. <br /> =Function <ref name="lu"/>=<br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> (8-oxoG, GO); this lesion is caused by oxidative attack by ROS on G. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions. hOGG1 is able to cleave the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase. hOGG1 has greater affinity for GO when is complementary to C, and also has catalytic activity towards other lesions such as formamidopyrimidines. <br /> =Structure=<br /> hOGG1 belongs to a super family of DNA repair enzymes that share a conserved two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate<ref name="lu"/>. This motif is necessary for interacting with DNA to recognize and catalyze the substrate <ref name ="Bruner">PMID: 10706276</ref>. As well, OGG1 is associated with two calcium ions that help stabilize the deformed DNA back bone at the site of the extruded lesion<ref name ="Bruner"/>.<br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>PMID: 11238177</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 <ref name="paper"> PMID: 15800616</ref>. <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref name= "GML">PMID: 15642264</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> where residues lining the pocket can directly interact to excise the lesion<ref name="paper"/>. <br /> =====Catalysis=====<br /> To excise GO, Lys 249 acts as a nucleophile attacking the C1' carbon in a SN1 reaction, when GO is inserted into the catalytic pocket<ref name= "GML"/>. Then hOGG1 AP lyase uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct, which undergoes a series of subsequent transformation resulting in DNA strand exscission on the 3’ side of the lesion<ref name= "GML"/>.<br /> =Implications of hOGG1=<br /> <br /> <br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1058116 8-Oxoguanine Glycosylase 2010-03-19T05:47:17Z

<p>Riley Hicks: </p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction<ref name="lu">PMID: 11892789</ref>=<br /> 8-Oxogunanine glycosylase (hOGG1) is a DNA glycosylase, coded from the OGG1 gene in humans; however, many homologs exist in different organisms and this enzyme was originally discovered in yeast. It is responsible for removing genotoxic lesions caused by oxidative damage in the presence of reactive oxygen species (ROS). Glycosylases, in general, are key enzymes for base excision repair and therefore maintaining integrity of DNA across the evolutionary spectrum. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases. <br /> =Function <ref name="lu"/>=<br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> (8-oxoG, GO); this lesion is caused by oxidative attack by ROS on G. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions. hOGG1 is able to cleave the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase. hOGG1 has greater affinity for GO when is complementary to C, and also has catalytic activity towards other lesions such as formamidopyrimidines. <br /> =Structure=<br /> hOGG1 belongs to a super family of DNA repair enzymes that share a conserved two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate<ref name="lu"/>. This motif is necessary for interacting with DNA to recognize and catalyze the substrate <ref name ="Bruner">PMID: 10706276</ref>. As well, OGG1 is associated with two calcium ions that help stabilize the deformed DNA back bone at the site of the extruded lesion<ref name ="Bruner"/>.<br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>PMID: 11238177</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 <ref name="paper"> PMID: 15800616</ref>. <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref name= "GML">PMID: 15642264</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> where residues lining the pocket can directly interact to excise the lesion<ref name="paper"/>. <br /> =====Catalysis=====<br /> To excise GO, Lys 249 acts as a nucleophile attacking the C1' carbon in a SN1 reaction, when GO is inserted into the catalytic pocket<ref name= "GML"/>. Then hOGG1 AP lyase uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct, which undergoes a series of subsequent transformation resulting in DNA strand exscission on the 3’ side of the lesion<ref name= "GML"/>.<br /> <br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1058115 8-Oxoguanine Glycosylase 2010-03-19T05:45:58Z

<p>Riley Hicks: </p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction=<br /> 8-Oxogunanine glycosylase (hOGG1) is a DNA glycosylase, coded from the OGG1 gene in humans; however, many homologs exist in different organisms and this enzyme was originally discovered in yeast. It is responsible for removing genotoxic lesions caused by oxidative damage in the presence of reactive oxygen species (ROS). Glycosylases, in general, are key enzymes for base excision repair and therefore maintaining integrity of DNA across the evolutionary spectrum. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases <ref name="lu">PMID: 11892789</ref>. <br /> =Function <ref name="lu"/>=<br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> (8-oxoG, GO); this lesion is caused by oxidative attack by ROS on G. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions. hOGG1 is able to cleave the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase. hOGG1 has greater affinity for GO when is complementary to C, and also has catalytic activity towards other lesions such as formamidopyrimidines. <br /> =Structure=<br /> hOGG1 belongs to a super family of DNA repair enzymes that share a conserved two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate<ref name="lu"/>. This motif is necessary for interacting with DNA to recognize and catalyze the substrate <ref name ="Bruner">PMID: 10706276</ref>. As well, OGG1 is associated with two calcium ions that help stabilize the deformed DNA back bone at the site of the extruded lesion<ref name ="Bruner"/>.<br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>PMID: 11238177</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 <ref name="paper"> PMID: 15800616</ref>. <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref name= "GML">PMID: 15642264</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> where residues lining the pocket can directly interact to excise the lesion<ref name="paper"/>. <br /> =====Catalysis=====<br /> To excise GO, Lys 249 acts as a nucleophile attacking the C1' carbon in a SN1 reaction, when GO is inserted into the catalytic pocket<ref name= "GML"/>. Then hOGG1 AP lyase uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct, which undergoes a series of subsequent transformation resulting in DNA strand exscission on the 3’ side of the lesion<ref name= "GML"/>.<br /> <br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1058113 8-Oxoguanine Glycosylase 2010-03-19T05:42:21Z

<p>Riley Hicks: /* Catalysis */</p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction=<br /> 8-Oxogunanine glycosylase (hOGG1) is a DNA glycosylase, coded from the OGG1 gene in humans. It is responsible for removing genotoxic lesions caused by oxidative damage in the presence of reactive oxygen species (ROS). Glycosylases, in general, are key enzymes for base excision repair and therefore maintaining integrity of DNA across the evolutionary spectrum. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases <ref name="lu">PMID: 11892789</ref>. <br /> =Function <ref name="lu"/>=<br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> (8-oxoG, GO); this lesion is caused by oxidative attack by ROS on G. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions. hOGG1 is able to cleave the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase. hOGG1 has greater affinity for GO when is complementary to C, and also has catalytic activity towards other lesions such as formamidopyrimidines. <br /> =Structure=<br /> hOGG1 belongs to a super family of DNA repair enzymes that share a conserved two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate<ref name="lu"/>. This motif is necessary for interacting with DNA to recognize and catalyze the substrate <ref name ="Bruner">PMID: 10706276</ref>. As well, OGG1 is associated with two calcium ions that help stabilize the deformed DNA back bone at the site of the extruded lesion<ref name ="Bruner"/>.<br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>PMID: 11238177</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 <ref name="paper"> PMID: 15800616</ref>. <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref name= "GML">PMID: 15642264</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> where residues lining the pocket can directly interact to excise the lesion<ref name="paper"/>. <br /> =====Catalysis=====<br /> To excise GO, Lys 249 acts as a nucleophile attacking the C1' carbon in a SN1 reaction, when GO is inserted into the catalytic pocket<ref name= "GML"/>. Then hOGG1 AP lyase uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct, which undergoes a series of subsequent transformation resulting in DNA strand exscission on the 3’ side of the lesion<ref name= "GML"/>.<br /> <br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1058111 8-Oxoguanine Glycosylase 2010-03-19T05:40:10Z

<p>Riley Hicks: </p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction=<br /> 8-Oxogunanine glycosylase (hOGG1) is a DNA glycosylase, coded from the OGG1 gene in humans. It is responsible for removing genotoxic lesions caused by oxidative damage in the presence of reactive oxygen species (ROS). Glycosylases, in general, are key enzymes for base excision repair and therefore maintaining integrity of DNA across the evolutionary spectrum. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases <ref name="lu">PMID: 11892789</ref>. <br /> =Function <ref name="lu"/>=<br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> (8-oxoG, GO); this lesion is caused by oxidative attack by ROS on G. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions. hOGG1 is able to cleave the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase. hOGG1 has greater affinity for GO when is complementary to C, and also has catalytic activity towards other lesions such as formamidopyrimidines. <br /> =Structure=<br /> hOGG1 belongs to a super family of DNA repair enzymes that share a conserved two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate<ref name="lu"/>. This motif is necessary for interacting with DNA to recognize and catalyze the substrate <ref name ="Bruner">PMID: 10706276</ref>. As well, OGG1 is associated with two calcium ions that help stabilize the deformed DNA back bone at the site of the extruded lesion<ref name ="Bruner"/>.<br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>PMID: 11238177</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 <ref name="paper"> PMID: 15800616</ref>. <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref name= "GML">PMID: 15642264</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> where residues lining the pocket can directly interact to excise the lesion<ref name="paper"/>. <br /> =====Catalysis=====<br /> To excise GO, Lys 249 acts as a nucleophile attacking the C1' carbon in a SN1 reaction, when GO is inserted into the catalytic pocket<ref name= "GML"/>. The AP lyase activity uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct, which undergoes a series of subsequent transformation resulting in DNA strand exscission on the 3’ side of the lesion<ref name= "GML"/>. <br /> <br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1058109 8-Oxoguanine Glycosylase 2010-03-19T05:37:59Z

<p>Riley Hicks: </p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction=<br /> 8-Oxogunanine glycosylase (hOGG1) is a DNA glycosylase, coded from the OGG1 gene in humans. It is responsible for removing genotoxic lesions caused by oxidative damage in the presence of reactive oxygen species (ROS). Glycosylases, in general, are key enzymes for base excision repair and therefore maintaining integrity of DNA across the evolutionary spectrum. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases <ref name="lu">PMID: 11892789</ref>. <br /> =Function <ref name="lu"/>=<br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> (8-oxoG, GO); this lesion is caused by oxidative attack by ROS on G. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions. hOGG1 is able to cleave the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase. hOGG1 has greater affinity for GO when is complementary to C, and also has catalytic activity towards other lesions such as formamidopyrimidines. <br /> =Structure=<br /> hOGG1 belongs to a super family of DNA repair enzymes that share a conserved two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate<ref name="lu"/>. This motif is necessary for interacting with DNA to recognize and catalyze the substrate <ref name ="Bruner">PMID: 10706276</ref>. As well, OGG1 is associated with two calcium ions that help stabilize the deformed DNA back bone at the site of the extruded lesion<ref name ="Bruner"/>.<br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>PMID: 11238177</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 <ref name="paper"> PMID: 15800616</ref>. <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref name= "GML">PMID: 15642264</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> where residues lining the pocket can directly interact to excise the lesion<ref name="paper"/>. <br /> =====Catalysis=====<br /> To excise GO, Lys 249 acts as a nucleophile attaching the C1' carbon in a SN1 when GO is inserted into the catalytic pocket<ref name= "GML"/>. The AP lyase activity uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct, which undergoes a series of subsequent transformation resulting in DNA strand exscission on the 3’ side of the lesion<ref name= "GML"/>. <br /> <br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1058108 8-Oxoguanine Glycosylase 2010-03-19T05:36:21Z

<p>Riley Hicks: </p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction=<br /> 8-Oxogunanine glycosylase (hOGG1) is a DNA glycosylase, coded from the OGG1 gene in humans. It is responsible for removing genotoxic lesions caused by oxidative damage in the presence of reactive oxygen species (ROS). Glycosylases, in general, are key enzymes for base excision repair and therefore maintaining integrity of DNA across the evolutionary spectrum. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases <ref name="lu">PMID: 11892789</ref>. <br /> =Function <ref name="lu"/>=<br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> (8-oxoG, GO); this lesion is caused by oxidative attack by ROS on G. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions. hOGG1 is able to cleave the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase. hOGG1 has greater affinity for GO when is complementary to C, and also has catalytic activity towards other lesions such as formamidopyrimidines. <br /> =Structure=<br /> hOGG1 belongs to a super family of DNA repair enzymes that share a conserved two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate<ref name="lu"/>. This motif is necessary for interacting with DNA to recognize and catalyze the substrate <ref name ="Bruner">PMID: 10706276</ref>. As well, OGG1 is associated with two calcium ions that help stabilize the deformed DNA back bone at the site of the extruded lesion<ref name ="Bruner"/>.<br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>PMID: 11238177</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 <ref name="paper"> PMID: 15800616</ref>. <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref name= "GML">PMID: 15642264</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> catalytic pocket where residues lining the pocket can directly interact to excise the lesion 7 <ref name="paper"/>. <br /> =====Catalysis=====<br /> To excise GO, Lys 249 acts as a nucleophile attaching the C1' carbon in a SN1 when GO is inserted into the catalytic pocket<ref name= "GML"/>. The AP lyase activity uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct, which undergoes a series of subsequent transformation resulting in DNA strand exscission on the 3’ side of the lesion<ref name= "GML"/>. <br /> <br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1058107 8-Oxoguanine Glycosylase 2010-03-19T05:34:23Z

<p>Riley Hicks: </p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction=<br /> 8-Oxogunanine glycosylase (hOGG1) is a DNA glycosylase, coded from the OGG1 gene in humans. It is responsible for removing genotoxic lesions caused by oxidative damage in the presence of reactive oxygen species (ROS). Glycosylases, in general, are key enzymes for base excision repair and therefore maintaining integrity of DNA across the evolutionary spectrum. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases <ref name="lu">PMID: 11892789</ref>. <br /> =Function <ref name="lu"/>=<br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> (8-oxoG, GO); this lesion is caused by oxidative attack by ROS on G. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions. hOGG1 is able to cleave the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase. hOGG1 has greater affinity for GO when is complementary to C, and also has catalytic activity towards other lesions such as formamidopyrimidines. <br /> =Structure=<br /> hOGG1 belongs to a super family of DNA repair enzymes that share a conserved two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate<ref name="lu"/>. This motif is necessary for interacting with DNA to recognize and catalyze the substrate <ref name ="Bruner">PMID: 10706276</ref>. As well, OGG1 is associated with two calcium ions that help stabilize the deformed DNA back bone at site of the turned out lesion<ref name ="Bruner"/>.<br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>PMID: 11238177</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 <ref name="paper"> PMID: 15800616</ref>. <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref name= "GML">PMID: 15642264</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> catalytic pocket where residues lining the pocket can directly interact to excise the lesion 7 <ref name="paper"/>. <br /> =====Catalysis=====<br /> To excise GO, Lys 249 acts as a nucleophile attaching the C1' carbon in a SN1 when GO is inserted into the catalytic pocket<ref name= "GML"/>. The AP lyase activity uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct, which undergoes a series of subsequent transformation resulting in DNA strand exscission on the 3’ side of the lesion<ref name= "GML"/>. <br /> <br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1058106 8-Oxoguanine Glycosylase 2010-03-19T05:32:29Z

<p>Riley Hicks: </p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction=<br /> 8-Oxogunanine glycosylase (hOGG1) is a DNA glycosylase, coded from the OGG1 gene in humans. It is responsible for removing genotoxic lesions caused by oxidative damage in the presence of reactive oxygen species (ROS). Glycosylases, in general, are key enzymes for base excision repair and therefore maintaining integrity of DNA across the evolutionary spectrum. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases <ref name="lu">PMID: 11892789</ref>. <br /> =Function <ref name="lu"/>=<br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> (8-oxoG, GO); this lesion is caused by oxidative attack by ROS on G. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions. hOGG1 is able to cleave the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase. hOGG1 has greater affinity for GO when is complementary to C, and also has catalytic activity towards other lesions such as formamidopyrimidines. <br /> =Structure=<br /> hOGG1 belongs to a super family of DNA repair enzymes that share a conserved two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate<ref name="lu"/>. This motif is necessary for interacting with DNA to recognize and catalyze the substrate <ref name ="Bruner">PMID: 10706276</ref>. As well, OGG1 is associated to two calcium ions that help to stabilize the deformed DNA back bone at site of the lesion<ref name ="Bruner"/>.<br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>PMID: 11238177</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 <ref name="paper"> PMID: 15800616</ref>. <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref name= "GML">PMID: 15642264</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> catalytic pocket where residues lining the pocket can directly interact to excise the lesion 7 <ref name="paper"/>. <br /> =====Catalysis=====<br /> To excise GO, Lys 249 acts as a nucleophile attaching the C1' carbon in a SN1 when GO is inserted into the catalytic pocket<ref name= "GML"/>. The AP lyase activity uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct, which undergoes a series of subsequent transformation resulting in DNA strand exscission on the 3’ side of the lesion<ref name= "GML"/>. <br /> <br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1058102 8-Oxoguanine Glycosylase 2010-03-19T05:27:55Z

<p>Riley Hicks: </p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction=<br /> 8-Oxogunanine glycosylase (hOGG1) is a DNA glycosylase, coded from the OGG1 gene in humans. It is responsible for removing genotoxic lesions caused by oxidative damage in the presence of reactive oxygen species. Glycosylases, in general, are key enzymes for base excision repair and therefore maintaining integrity of DNA across the evolutionary spectrum. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases <ref name="lu">PMID: 11892789</ref>. <br /> =Function <ref name="lu"/>=<br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> (8-oxoG, GO); this lesion is caused by oxidative attack from reactive species produced during normal metabolism. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions. hOGG1 cleaves the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase. hOGG1 has greater affinity for GO that is complementary to C, and also has catalytic activity towards other lesions such as formamidopyrimidines. <br /> =Structure=<br /> hOGG1 belongs to a super family of DNA repair enzymes that share a conserved two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate<ref name="lu"/>. This motif is necessary for interacting with DNA to recognize and catalyze the substrate <ref name ="Bruner">PMID: 10706276</ref>. As well, OGG1 is associated to two calcium ions that help to stabilize the deformed DNA back bone at site of the lesion<ref name ="Bruner"/>.<br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>PMID: 11238177</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 <ref name="paper"> PMID: 15800616</ref>. <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref name= "GML">PMID: 15642264</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> catalytic pocket where residues lining the pocket can directly interact to excise the lesion 7 <ref name="paper"/>. <br /> =====Catalysis=====<br /> To excise GO, Lys 249 acts as a nucleophile attaching the C1' carbon in a SN1 when GO is inserted into the catalytic pocket<ref name= "GML"/>. The AP lyase activity uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct, which undergoes a series of subsequent transformation resulting in DNA strand exscission on the 3’ side of the lesion<ref name= "GML"/>. <br /> <br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1058101 8-Oxoguanine Glycosylase 2010-03-19T05:26:07Z

<p>Riley Hicks: </p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction=<br /> 8-Oxogunanine glycosylase (hOGG1) is a DNA glycosylase, coded from the OGG1 gene in humans. It is responsible for removing genotoxic lesions caused by oxidative damage in the presence of reactive oxygen species. Glycosylases, in general, are key enzymes for base excision repair and therefore maintaining integrity of DNA across the evolutionary spectrum. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases <ref name="lu">PMID: 11892789</ref>. <br /> =Function <ref name="lu"/>=<br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> 7,8-dihydro-8-oxogunanine (8-oxoG, GO); this lesion is caused by oxidative attack from reactive species produced during normal metabolism. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions. hOGG1 cleaves the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase. hOGG1 has greater affinity for GO that is complementary to C, and also has catalytic activity towards other lesions such as formamidopyrimidines. <br /> =Structure=<br /> hOGG1 belongs to a super family of DNA repair enzymes that share a conserved two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate<ref name="lu"/>. This motif is necessary for interacting with DNA to recognize and catalyze the substrate <ref name ="Bruner">PMID: 10706276</ref>. As well, OGG1 is associated to two calcium ions that help to stabilize the deformed DNA back bone at site of the lesion<ref name ="Bruner"/>.<br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>PMID: 11238177</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 <ref name="paper"> PMID: 15800616</ref>. <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref name= "GML">PMID: 15642264</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> catalytic pocket where residues lining the pocket can directly interact to excise the lesion 7 <ref name="paper"/>. <br /> =====Catalysis=====<br /> To excise GO, Lys 249 acts as a nucleophile attaching the C1' carbon in a SN1 when GO is inserted into the catalytic pocket<ref name= "GML"/>. The AP lyase activity uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct, which undergoes a series of subsequent transformation resulting in DNA strand exscission on the 3’ side of the lesion<ref name= "GML"/>. <br /> <br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1058100 8-Oxoguanine Glycosylase 2010-03-19T05:23:34Z

<p>Riley Hicks: </p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction=<br /> 8-Oxogunanine glycosylase (hOGG1) is a DNA glycosylase, coded from the OGG1 gene in humans. It is responsible for removing genotoxic lesions caused by oxidative damage in the presence of reactive oxygen species. Glycosylases, in general, are important enzymes for base excision repair. This repair system is responsible for maintaining the integrity of DNA across the evolutionary spectrum. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases <ref name="lu">PMID: 11892789</ref>. <br /> =Function <ref name="lu"/>=<br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> 7,8-dihydro-8-oxogunanine (8-oxoG, GO); this lesion is caused by oxidative attack from reactive species produced during normal metabolism. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions. hOGG1 cleaves the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase. hOGG1 has greater affinity for GO that is complementary to C, and also has catalytic activity towards other lesions such as formamidopyrimidines. <br /> =Structure=<br /> hOGG1 belongs to a super family of DNA repair enzymes that share a conserved two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate<ref name="lu"/>. This motif is necessary for interacting with DNA to recognize and catalyze the substrate <ref name ="Bruner">PMID: 10706276</ref>. As well, OGG1 is associated to two calcium ions that help to stabilize the deformed DNA back bone at site of the lesion<ref name ="Bruner"/>.<br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>PMID: 11238177</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 <ref name="paper"> PMID: 15800616</ref>. <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref name= "GML">PMID: 15642264</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> catalytic pocket where residues lining the pocket can directly interact to excise the lesion 7 <ref name="paper"/>. <br /> =====Catalysis=====<br /> To excise GO, Lys 249 acts as a nucleophile attaching the C1' carbon in a SN1 when GO is inserted into the catalytic pocket<ref name= "GML"/>. The AP lyase activity uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct, which undergoes a series of subsequent transformation resulting in DNA strand exscission on the 3’ side of the lesion<ref name= "GML"/>. <br /> <br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1058099 8-Oxoguanine Glycosylase 2010-03-19T05:22:37Z

<p>Riley Hicks: </p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction=<br /> 8-Oxogunanine glycosylase (hOGG1) is a DNA glycosylase, coded from the OGG1 gene in humans. It is responsible for removing lesions genotoxic caused by oxidative damage in the presence of reactive oxygen species. Glycosylases, in general, are important enzymes for base excision repair. This repair system is responsible for maintaining the integrity of DNA across the evolutionary spectrum. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases <ref name="lu">PMID: 11892789</ref>. <br /> =Function <ref name="lu"/>=<br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> 7,8-dihydro-8-oxogunanine (8-oxoG, GO); this lesion is caused by oxidative attack from reactive species produced during normal metabolism. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions. hOGG1 cleaves the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase. hOGG1 has greater affinity for GO that is complementary to C, and also has catalytic activity towards other lesions such as formamidopyrimidines. <br /> =Structure=<br /> hOGG1 belongs to a super family of DNA repair enzymes that share a conserved two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate<ref name="lu"/>. This motif is necessary for interacting with DNA to recognize and catalyze the substrate <ref name ="Bruner">PMID: 10706276</ref>. As well, OGG1 is associated to two calcium ions that help to stabilize the deformed DNA back bone at site of the lesion<ref name ="Bruner"/>.<br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>PMID: 11238177</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 <ref name="paper"> PMID: 15800616</ref>. <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref name= "GML">PMID: 15642264</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> catalytic pocket where residues lining the pocket can directly interact to excise the lesion 7 <ref name="paper"/>. <br /> =====Catalysis=====<br /> To excise GO, Lys 249 acts as a nucleophile attaching the C1' carbon in a SN1 when GO is inserted into the catalytic pocket<ref name= "GML"/>. The AP lyase activity uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct, which undergoes a series of subsequent transformation resulting in DNA strand exscission on the 3’ side of the lesion<ref name= "GML"/>. <br /> <br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1058097 8-Oxoguanine Glycosylase 2010-03-19T05:15:50Z

<p>Riley Hicks: </p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction=<br /> 8-Oxogunanine glycosylase (hOGG1) is a DNA glycosylase, coded from the OGG1 gene in humans. It is responsible for removing lesions genotoxic caused by oxidative damage in the presence of reactive oxygen species. Glycosylases, in general, are important enzymes for base excision repair. This repair system is responsible for maintaining the integrity of DNA across the evolutionary spectrum. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases <ref name="lu">PMID: 11892789</ref>. <br /> =Function <ref name="lu"/>=<br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> 7,8-dihydro-8-oxogunanine (8-oxoG, GO); this lesion is caused by oxidative attack from reactive species produced during normal metabolism. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions. hOGG1 cleaves the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase. hOGG1 has greater affinity for GO that is complementary to C, and also has catalytic activity towards other lesions such as formamidopyrimidines. <br /> =Structure=<br /> hOGG1 belongs to a super family of DNA repair enzymes that share a conserved two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate(2). This motif is necessary for interacting with DNA to recognize and catalyze the substrate (5). As well, OGG1 is associated to two calcium ions that help to stabilize the deformed DNA back bone at site of the lesion.<br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>PMID: 11238177</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 <ref name="paper"> PMID: 15800616</ref>. <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref name= "GML">PMID: 15642264</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> catalytic pocket where residues lining the pocket can directly interact to excise the lesion 7 <ref name="paper"/>. <br /> =====Catalysis=====<br /> To excise GO, Lys 249 acts as a nucleophile attaching the C1' carbon in a SN1 when GO is inserted into the catalytic pocket<ref name= "GML"/>. The AP lyase activity uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct, which undergoes a series of subsequent transformation resulting in DNA strand exscission on the 3’ side of the lesion<ref name= "GML"/>. <br /> <br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1058095 8-Oxoguanine Glycosylase 2010-03-19T04:53:24Z

<p>Riley Hicks: </p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction=<br /> 8-Oxogunanine glycosylase (hOGG1) is a DNA glycosylase, coded from the OGG1 gene in humans. It is responsible for removing lesions genotoxic caused by oxidative damage in the presence of reactive oxygen species. Glycosylases, in general, are important enzymes for base excision repair. This repair system is responsible for maintaining the integrity of DNA across the evolutionary spectrum. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases <ref name="lu">PMID: 11892789</ref>. <br /> =Function <ref name="lu"/>=<br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> 7,8-dihydro-8-oxogunanine (8-oxoG, GO); this lesion is caused by oxidative attack from reactive species produced during normal metabolism. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions. hOGG1 cleaves the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase. hOGG1 has greater affinity for GO that is complementary to C, and also has catalytic activity towards other lesions such as formamidopyrimidines. <br /> =Structure=<br /> hOGG1 belongs to a super family of DNA repair enzymes that share a conserved two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate(2). This motif is necessary for interacting with DNA to recognize and catalyze the substrate (5). As well, OGG1 is associated to two calcium ions that help to stabilize the deformed DNA back bone at site of the lesion.<br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>PMID: 11238177</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 <ref name="paper"> PMID: 15800616</ref>. <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref>PMID: 15642264</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> catalytic pocket where residues lining the pocket can directly interact to excise the lesion 7 <ref name="paper"/>. <br /> =====Catalysis=====<br /> To excise the base, the conserved aspartate (ASP 268) activates Lys 249 to form a schiff base intermediate <ref name="lu"/>. This acts as a nucleophile attaching the C1' carbon in a SN1 fashion to remove GO<ref name="lu"/>. The AP lyase activity uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct, which undergoes a series of subsequent transformation resulting in DNA strand exscission on the 3’ side of the lesion. <br /> <br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1058094 8-Oxoguanine Glycosylase 2010-03-19T04:52:28Z

<p>Riley Hicks: </p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction=<br /> 8-Oxogunanine glycosylase (hOGG1) is a DNA glycosylase, coded from the OGG1 gene in humans. It is responsible for removing lesions genotoxic caused by oxidative damage in the presence of reactive oxygen species. Glycosylases, in general, are important enzymes for base excision repair. This repair system is responsible for maintaining the integrity of DNA across the evolutionary spectrum. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases <ref name="lu">PMID: 11892789</ref>. <br /> =Function <ref name="lu"/>=<br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> 7,8-dihydro-8-oxogunanine (8-oxoG, GO); this lesion is caused by oxidative attack from reactive species produced during normal metabolism. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions. hOGG1 cleaves the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase. hOGG1 has greater affinity for GO that is complementary to C, and also has catalytic activity towards other lesions such as formamidopyrimidines. <br /> =Structure=<br /> hOGG1 belongs to a super family of DNA repair enzymes that share a conserved two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate(2). This motif is necessary for interacting with DNA to recognize and catalyze the substrate (5). As well, OGG1 is associated to two calcium ions that help to stabilize the deformed DNA back bone at site of the lesion.<br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>PMID: 11238177</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 <ref name="paper"> PMID: 15800616</ref>. <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref>PMID: 15642264</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> catalytic pocket where residues lining the pocket can directly interact to excise the lesion 7 <ref name="paper"/>. <br /> =====Catalysis=====<br /> To excise the base, the conserved aspartate (ASP 268) activates Lys 249 to form a schiff base intermediate <ref name="lu"/>. This acts as a nucleophile attaching the C1' carbon in a SN1 fashion to remove Go<ref name="lu"/>. The AP lyase activity uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct, which undergoes a series of subsequent transformation resulting in DNA strand exscission on the 3’ side of the lesion. <br /> <br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1058093 8-Oxoguanine Glycosylase 2010-03-19T04:51:07Z

<p>Riley Hicks: </p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction=<br /> 8-Oxogunanine glycosylase (hOGG1) is a DNA glycosylase, coded from the OGG1 gene in humans. It is responsible for removing lesions genotoxic caused by oxidative damage in the presence of reactive oxygen species. Glycosylases, in general, are important enzymes for base excision repair. This repair system is responsible for maintaining the integrity of DNA across the evolutionary spectrum. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases <ref name="lu">PMID: 11892789</ref>. <br /> =Function <ref name="lu"/>=<br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> 7,8-dihydro-8-oxogunanine (8-oxoG, GO); this lesion is caused by oxidative attack from reactive species produced during normal metabolism. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions. hOGG1 cleaves the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase. hOGG1 has greater affinity for GO that is complementary to C, and also has catalytic activity towards other lesions such as formamidopyrimidines. <br /> =Structure=<br /> hOGG1 belongs to a super family of DNA repair enzymes that share a conserved two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate(2). This motif is necessary for interacting with DNA to recognize and catalyze the substrate (5). As well, OGG1 is associated to two calcium ions that help to stabilize the deformed DNA back bone at site of the lesion.<br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>PMID: 11238177</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 <ref name="paper"> PMID: 15800616</ref>. <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref> A DNA Glycosylase from Pyrobaculum aerophilum with an 8-Oxoguanine Binding Mode and a Noncanonical Helix-Hairpin-Helix Structure/ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> catalytic pocket where residues lining the pocket can directly interact to excise the lesion 7 <ref name="paper"/>. <br /> =====Catalysis=====<br /> To excise the base, the conserved aspartate (ASP 268) activates Lys 249 to form a schiff base intermediate <ref name="lu"/>. This acts as a nucleophile attaching the C1' carbon in a SN1 fashion to remove Go<ref name="lu"/>. The AP lyase activity uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct, which undergoes a series of subsequent transformation resulting in DNA strand exscission on the 3’ side of the lesion. <br /> <br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1058092 8-Oxoguanine Glycosylase 2010-03-19T04:40:32Z

<p>Riley Hicks: </p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction=<br /> 8-Oxogunanine glycosylase (hOGG1) is a DNA glycosylase, coded from the OGG1 gene in humans. It is responsible for removing lesions genotoxic caused by oxidative damage in the presence of reactive oxygen species. Glycosylases, in general, are important enzymes for base excision repair. This repair system is responsible for maintaining the integrity of DNA across the evolutionary spectrum. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases <ref name="lu">PMID: 11892789</ref>. <br /> =Function <ref name="lu"/>=<br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> 7,8-dihydro-8-oxogunanine (8-oxoG, GO); this lesion is caused by oxidative attack from reactive species produced during normal metabolism. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions. hOGG1 cleaves the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase. hOGG1 has greater affinity for GO that is complementary to C, and also has catalytic activity towards other lesions such as formamidopyrimidines. <br /> =Structure=<br /> hOGG1 belongs to a super family of DNA repair enzymes that share a conserved two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate(2). This motif is necessary for interacting with DNA to recognize and catalyze the substrate (5). As well, OGG1 is associated to two calcium ions that help to stabilize the deformed DNA back bone at site of the lesion.<br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>PMID: 11238177</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 <ref name="paper"> PMID: 15800616</ref>. <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref> Structure Vol.13, 87-98</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> catalytic pocket where residues lining the pocket can directly interact to excise the lesion 7 <ref name="paper"/>. <br /> =====Catalysis=====<br /> To excise the base, the conserved aspartate (ASP 268) activates Lys 249 to form a schiff base intermediate <ref name="lu"/>. This acts as a nucleophile attaching the C1' carbon in a SN1 fashion to remove Go<ref name="lu"/>. The AP lyase activity uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct, which undergoes a series of subsequent transformation resulting in DNA strand exscission on the 3’ side of the lesion. <br /> <br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1058006 8-Oxoguanine Glycosylase 2010-03-19T00:49:40Z

<p>Riley Hicks: </p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction=<br /> 8-Oxogunanine glycosylase (hOGG1) is a DNA glycosylase, coded from the OGG1 gene in humans. It is responsible for removing lesions genotoxic caused by oxidative damage in the presence of reactive oxygen species. Glycosylases, in general, are important enzymes for base excision repair. This repair system is responsible for maintaining the integrity of DNA across the evolutionary spectrum. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases <ref name="lu">PMID: 11892789</ref>. <br /> =Function=<br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> 7,8-dihydro-8-oxogunanine (8-oxoG, GO); this lesion is caused by oxidative attack from reactive species produced during normal metabolism. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions. hOGG1 cleaves the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase. hOGG1 has greater affinity for GO that is complementary to C, and also has catalytic activity towards other lesions such as formamidopyrimidines. <br /> =Structure=<br /> hOGG1 belongs to a super family of DNA repair enzymes that share a conserved two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate(2). This motif is necessary for interacting with DNA to recognize and catalyze the substrate (5). As well, OGG1 is associated to two calcium ions that help to stabilize the deformed DNA back bone at site of the lesion.<br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>Capelli et. al</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 <ref name="paper"> PMID: 15800616</ref>. <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref> Structure Vol.13, 87-98</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> catalytic pocket where residues lining the pocket can directly interact to excise the lesion 7 <ref name="paper"/>. <br /> =====Catalysis=====<br /> To excise the base, the conserved aspartate (ASP 268) activates Lys 249 to form a schiff base intermediate <ref name="lu"/>. This acts as a nucleophile attaching the C1' carbon in a SN1 fashion to remove Go<ref name="lu"/>. The AP lyase activity uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct, which undergoes a series of subsequent transformation resulting in DNA strand exscission on the 3’ side of the lesion. <br /> <br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1058003 8-Oxoguanine Glycosylase 2010-03-19T00:44:02Z

<p>Riley Hicks: </p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction=<br /> 8-Oxogunanine glycosylase (hOGG1) is a DNA glycosylase, coded from the OGG1 gene in humans. It is responsible for removing lesions genotoxic caused by oxidative damage in the presence of reactive oxygen species. Glycosylases, in general, are important enzymes for base excision repair. This repair system is responsible for maintaining the integrity of DNA across the evolutionary spectrum. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases <ref name="lu">PMID: 11892789</ref>. <br /> =Function=<br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> 7,8-dihydro-8-oxogunanine (8-oxoG, GO); this lesion is caused by oxidative attack from reactive species produced during normal metabolism. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions. hOGG1 cleaves the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase. hOGG1 has greater affinity for GO that is complementary to C, and also has catalytic activity towards other lesions such as formamidopyrimidines. <br /> =Structure=<br /> hOGG1 belongs to a super family of DNA repair enzymes that share a conserved two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate(2). This motif is necessary for interacting with DNA to recognize and catalyze the substrate (5). As well, OGG1 is associated to two calcium ions that help to stabilize the deformed DNA back bone at site of the lesion.<br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>Capelli et. al</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 <ref name="paper"> PMID: 15800616</ref>. <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref> Structure Vol.13, 87-98</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> catalytic pocket where residues lining the pocket can directly interact to excise the lesion 7 <ref name="paper">. <br /> =====Catalysis=====<br /> To excise the base, the conserved aspartate (ASP 268) activates Lys 249 to form a schiff base intermediate <ref name="lu"/>. This acts as a nucleophile attaching the C1' carbon in a SN1 fashion to remove Go<ref name="lu"/>. The AP lyase activity uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct, which undergoes a series of subsequent transformation resulting in DNA strand exscission on the 3’ side of the lesion. <br /> <br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1057999 8-Oxoguanine Glycosylase 2010-03-19T00:35:39Z

<p>Riley Hicks: </p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction=<br /> 8-Oxogunanine glycosylase (hOGG1) is a DNA glycosylase, coded from the OGG1 gene in humans. It is responsible for removing lesions genotoxic caused by oxidative damage in the presence of reactive oxygen species. Glycosylases, in general, are important enzymes for base excision repair. This repair system is responsible for maintaining the integrity of DNA across the evolutionary spectrum. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases <ref name="lu">PMID: 11892789</ref>. <br /> =Function<ref name="lu"/>=<br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> 7,8-dihydro-8-oxogunanine (8-oxoG, GO); this lesion is caused by oxidative attack from reactive species produced during normal metabolism. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions. hOGG1 cleaves the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase. hOGG1 has greater affinity for GO that is complementary to C, and also has catalytic activity towards other lesions such as formamidopyrimidines. <br /> =Structure=<br /> hOGG1 belongs to a super family of DNA repair enzymes that share a conserved two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate(2). This motif is necessary for interacting with DNA to recognize and catalyze the substrate (5). As well, OGG1 is associated to two calcium ions that help to stabilize the deformed DNA back bone at site of the lesion.<br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>Capelli et. al</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 <ref name="paper"> PMID: 15800616</ref>. <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref> Structure Vol.13, 87-98</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> catalytic pocket where residues lining the pocket can directly interact to excise the lesion 7 <ref name="paper">. <br /> =====Catalysis=====<br /> To excise the base, the conserved aspartate (ASP 268) activates Lys 249 to form a schiff base intermediate <ref name="lu"/>. This acts as a nucleophile attaching the C1' carbon in a SN1 fashion to remove Go<ref name="lu"/>. The AP lyase activity uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct, which undergoes a series of subsequent transformation resulting in DNA strand exscission on the 3’ side of the lesion. <br /> <br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1057995 8-Oxoguanine Glycosylase 2010-03-19T00:29:28Z

<p>Riley Hicks: </p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction=<br /> 8-Oxogunanine glycosylase (hOGG1) is a DNA glycosylase, coded from the OGG1 gene in humans. It is responsible for removing lesions genotoxic caused by oxidative damage in the presence of reactive oxygen species. Glycosylases, in general, are important enzymes for base excision repair. This repair system is responsible for maintaining the integrity of DNA across the evolutionary spectrum. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases <ref name="lu">PMID: 11892789</ref>. <br /> =Function<ref name="lu"/>=<br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> 7,8-dihydro-8-oxogunanine (8-oxoG, GO); this lesion is caused by oxidative attack from reactive species produced during normal metabolism. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions. hOGG1 cleaves the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase. hOGG1 has greater affinity for GO that is complementary to C, and also has catalytic activity towards other lesions such as formamidopyrimidines. <br /> =Structure=<br /> hOGG1 belongs to a super family of DNA repair enzymes that share a conserved two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate(2). This motif is necessary for interacting with DNA to recognize and catalyze the substrate (5). As well, OGG1 is associated to two calcium ions that help to stabilize the deformed DNA back bone at site of the lesion.<br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>Capelli et. al</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 (the paper). <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref> Structure Vol.13, 87-98</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> catalytic pocket where residues lining the pocket can directly interact to excise the lesion (7,t`he paper). <br /> =====Catalysis=====<br /> To excise the base, the conserved aspartate (ASP 268) activates Lys 249 to form a schiff base intermediate <ref name="lu"/>. This acts as a nucleophile attaching the C1' carbon in a SN1 fashion to remove Go<ref name="lu"/>. The AP lyase activity uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct, which undergoes a series of subsequent transformation resulting in DNA strand exscission on the 3’ side of the lesion. <br /> <br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1057994 8-Oxoguanine Glycosylase 2010-03-19T00:27:18Z

<p>Riley Hicks: </p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction=<br /> 8-Oxogunanine glycosylase (hOGG1) is a DNA glycosylase, coded from the OGG1 gene in humans. It is responsible for removing lesions genotoxic caused by oxidative damage in the presence of reactive oxygen species. Glycosylases, in general, are important enzymes for base excision repair. This repair system is responsible for maintaining the integrity of DNA across the evolutionary spectrum. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases <ref name="lu">PMID: 11892789</ref>. <br /> =Function<ref name="lu"/>=<br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> 7,8-dihydro-8-oxogunanine (8-oxoG, GO); this lesion is caused by oxidative attack from reactive species produced during normal metabolism. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions. hOGG1 cleaves the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase. hOGG1 has greater affinity for GO that is complementary to C, and also has catalytic activity towards other lesions such as formamidopyrimidines. <br /> =Structure=<br /> hOGG1 belongs to a super family of DNA repair enzymes that share a conserved two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate(2). This motif is necessary for interacting with DNA to recognize and catalyze the substrate (5). As well, OGG1 is associated to two calcium ions that help to stabilize the deformed DNA back bone at site of the lesion.<br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>Capelli et. al</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 (the paper). <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref> Structure Vol.13, 87-98</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> catalytic pocket where residues lining the pocket can directly interact to excise the lesion (7,t`he paper). <br /> =====Catalysis=====<br /> To excise the base, the conserved aspartate (ASP 268) activates Lys 249 to form a schiff base intermediate <ref>PMID: 11892789</ref>. This acts as a nucleophile attaching the C1' carbon in a SN1 fashion to remove Go <ref>PMID: 11892789</ref>. The AP lyase activity uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct, which undergoes a series of subsequent transformation resulting in DNA strand exscission on the 3’ side of the lesion. <br /> <br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1057991 8-Oxoguanine Glycosylase 2010-03-19T00:04:14Z

<p>Riley Hicks: </p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction=<br /> 8-Oxogunanine glycosylase (hOGG1) is a DNA glycosylase, coded from the OGG1 gene in humans. It is responsible for removing lesions genotoxic caused by oxidative damage in the presence of reactive oxygen species. Glycosylases, in general, are important enzymes for base excision repair. This repair system is responsible for maintaining the integrity of DNA across the evolutionary spectrum. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases (1).<br /> =Function= <br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> 7,8-dihydro-8-oxogunanine (8-oxoG, GO); this lesion is caused by oxidative attack from reactive species produced during normal metabolism. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions. hOGG1 cleaves the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase. hOGG1 has greater affinity for GO that is complementary to C, and also has catalytic activity towards other lesions such as formamidopyrimidines. <br /> =Structure=<br /> hOGG1 belongs to a super family of DNA repair enzymes that share a conserved two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate(2). This motif is necessary for interacting with DNA to recognize and catalyze the substrate (5). As well, OGG1 is associated to two calcium ions that help to stabilize the deformed DNA back bone at site of the lesion.<br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>Capelli et. al</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 (the paper). <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref> Structure Vol.13, 87-98</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> catalytic pocket where residues lining the pocket can directly interact to excise the lesion (7,t`he paper). <br /> =====Catalysis=====<br /> To excise the base, the conserved aspartate (ASP 268) activates Lys 249 to form a schiff base intermediate. This acts as a nucleophile attaching the C1' carbon in a SN1 fashion to remove Go (1). The AP lyase activity uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct, which undergoes a series of subsequent transformation resulting in DNA strand exscission on the 3’ side of the lesion. <br /> <br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1057990 8-Oxoguanine Glycosylase 2010-03-19T00:00:18Z

<p>Riley Hicks: </p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction=<br /> 8-Oxogunanine glycosylase (hOGG1) is a DNA glycosylase, coded from the OGG1 gene in humans. It is responsible for removing lesions genotoxic caused by oxidative damage in the presence of reactive oxygen species. Glycosylases, in general, are important enzymes for base excision repair. This repair system is responsible for maintaining the integrity of DNA across the evolutionary spectrum. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand; however, if it is not repaired mutagenesis occurs possibly leading to cancer and other degenerative diseases (1).<br /> =Function= <br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> 7,8-dihydro-8-oxogunanine (8-oxoG, GO); this lesion is caused by oxidative attack from reactive species produced during normal metabolism. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions. hOGG1 cleaves the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase. hOGG1 has greater affinity for GO that is complementary to C, and also has catalytic activity towards other lesions such as formamidopyrimidines. <br /> =Structure=<br /> hOGG1 belongs to a super family of DNA repair enzymes that share a conserved two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate(2). This motif is necessary for interacting with DNA to recognize and catalyze the substrate (5).<br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>Capelli et. al</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 (the paper). <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref> Structure Vol.13, 87-98</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> catalytic pocket where residues lining the pocket can directly interact to excise the lesion (7,t`he paper). <br /> =====Catalysis=====<br /> To excise the base, the conserved aspartate (ASP 268) activates Lys 249 to form a schiff base intermediate. This acts as a nucleophile attaching the C1' carbon in a SN1 fashion to remove Go (1). The AP lyase activity uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct, which undergoes a series of subsequent transformation resulting in DNA strand exscission on the 3’ side of the lesion. <br /> <br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1057987 8-Oxoguanine Glycosylase 2010-03-18T23:26:11Z

<p>Riley Hicks: </p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction=<br /> 8-Oxogunanine glycosylase (hOGG1) is a DNA glycosylase, coded from the OGG1 gene in humans. It is responsible for removing lesions genotoxic caused by oxidative damage. Glycosylases, in general, are important enzymes for base excision repair. This repair system is responsible for maintaining the integrity of DNA across the evolutionary spectrum. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand (1).<br /> =Function= <br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> 7,8-dihydro-8-oxogunanine (8-oxoG, GO); this lesion is caused by oxidative attack from reactive species produced during normal metabolism. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions. hOGG1 cleaves the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase. hOGG1 has greater affinity for GO that is complementary to C, and also has catalytic activity towards other lesions such as formamidopyrimidines. <br /> =Structure=<br /> hOGG1 belongs to a super family of DNA repair enzymes that share a conserved two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate(2). This motif is necessary for interacting with DNA to recognize and catalyze the substrate (5).<br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>Capelli et. al</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 (the paper). <br /> =====Recognition=====<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref> Structure Vol.13, 87-98</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> catalytic pocket where residues lining the pocket can directly interact to excise the lesion (7,t`he paper). <br /> =====Catalysis=====<br /> To excise the base, the conserved aspartate (ASP 268) activates Lys 249 to form a schiff base intermediate. This acts as a nucleophile attaching the C1' carbon in a SN1 fashion to remove Go (1). The AP lyase activity uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct, which undergoes a series of subsequent transformation resulting in DNA strand exscission on the 3’ side of the lesion. <br /> <br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1057986 8-Oxoguanine Glycosylase 2010-03-18T23:24:58Z

<p>Riley Hicks: </p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction=<br /> 8-Oxogunanine glycosylase (hOGG1) is a DNA glycosylase, coded from the OGG1 gene in humans. It is responsible for removing lesions genotoxic caused by oxidative damage. Glycosylases, in general, are important enzymes for base excision repair. This repair system is responsible for maintaining the integrity of DNA across the evolutionary spectrum. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand (1).<br /> =Function= <br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> 7,8-dihydro-8-oxogunanine (8-oxoG, GO); this lesion is caused by oxidative attack from reactive species produced during normal metabolism. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions. hOGG1 cleaves the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase. hOGG1 has greater affinity for GO that is complementary to C, and also has catalytic activity towards other lesions such as formamidopyrimidines. <br /> =Structure=<br /> hOGG1 belongs to a super family of DNA repair enzymes that share a conserved two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate(2). This motif is necessary for interacting with DNA to recognize and catalyze the substrate (5).<br /> =Mechanism= <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>Capelli et. al</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to catalyze GO and discriminate between GO and G even though they differ only at the C8 and N7 (the paper). <br /> ==Recognition==<br /> hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref> Structure Vol.13, 87-98</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> catalytic pocket where residues lining the pocket can directly interact to excise the lesion (7,t`he paper). <br /> ==Catalysis==<br /> To excise the base, the conserved aspartate (ASP 268) activates Lys 249 to form a schiff base intermediate. This acts as a nucleophile attaching the C1' carbon in a SN1 fashion to remove Go (1). The AP lyase activity uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct, which undergoes a series of subsequent transformation resulting in DNA strand exscission on the 3’ side of the lesion. <br /> <br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1057976 8-Oxoguanine Glycosylase 2010-03-18T21:25:54Z

<p>Riley Hicks: </p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction=<br /> 8-Oxogunanine glycosylase (hOGG1) is a DNA glycosylase, coded from the OGG1 gene in humans. It is responsible for removing lesions genotoxic caused by oxidative damage. Glycosylases, in general, are important enzymes for base excision repair. This repair system is responsible for maintaining the integrity of DNA across the evolutionary spectrum. Once a lesion is successfully excised, the transcription machinery of the cell can repair the DNA strand (1).<br /> =Function= <br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> 7,8-dihydro-8-oxogunanine (8-oxoG, GO); this lesion is caused by oxidative attack from reactive species produced during normal metabolism. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions. hOGG1 cleaves the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase. hOGG1 has greater affinity for GO that is complementary to C, and also has catalytic activity towards other lesions such as formamidopyrimidines. <br /> =Structure and Mechanism=<br /> <br /> hOGG1 belongs to a super family of DNA repair enzymes that share a conserved two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate(2). This motif is necessary for interacting with DNA to recognize and catalyze the substrate (5).<br /> <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>Capelli et. al</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to discriminate between GO and G even though they differ at the C8 and N7 (the paper). hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref> Structure Vol.13, 87-98</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> catalytic pocket where residues lining the pocket can directly interact to excise the lesion (7,the paper). The AP lyase activity uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct, which undergoes a series of subsequent transformation resulting in DNA strand exscission on the 3’ side of the lesion. <br /> <br /> =References=<br /> <references/></div>

Riley Hicks https://proteopedia.org/index.php?title=8-Oxoguanine_Glycosylase&diff=1057975 8-Oxoguanine Glycosylase 2010-03-18T21:24:02Z

<p>Riley Hicks: </p> <hr /> <div>{{STRUCTURE_1yqr| PDB=1yqr | SCENE= }}<br /> '''8-Oxoguanine Glycosylase<br><br /> =Introduction=<br /> 8-Oxogunanine glycosylase (hOGG1) is a DNA glycosylase, coded from the OGG1 gene in humans. It is responsible for removing lesions genotoxic caused by oxidative damage. Glycosylases, in general, are important enzymes for base excision repair. This repair system is responsible for maintaining the integrity of DNA across the evolutionary spectrum.<br /> =Function= <br /> hOGG1 repairs <scene name='Sandbox_164/Scene_3/1'>7,8-dihydro-8-oxogunanine</scene> 7,8-dihydro-8-oxogunanine (8-oxoG, GO); this lesion is caused by oxidative attack from reactive species produced during normal metabolism. It is a particularly dangerous, and stable mutation because GO can Hoogsteen base-pair with adenine causing G:C to T:A tranversions. hOGG1 cleaves the N-glycosylic bond between the deoxyribose moiety and GO leaving an apurinic-apyrimdinic (AP) site. It also has is the intrinsic ability to cleave the 3’ phosphodiester of the AP site by β-elimination, acting as an AP lyase, and making it a bifunctional glycosylase. hOGG1 has greater affinity for GO that is complementary to C, and also has catalytic activity towards other lesions such as formamidopyrimidines. <br /> =Structure and Mechanism=<br /> <br /> hOGG1 belongs to a super family of DNA repair enzymes that share a conserved two-domain fold containing a <scene name='Sandbox_164/Scene_2/2'>helix-hairpin-helix</scene> DNA binding motif followed by a Glycine/Proline rich stretch and a invariant Aspartate(2). This motif is necessary for interacting with DNA to recognize and catalyze the substrate (5).<br /> <br /> Only 50,000 hOGG1 molecules protect the entire 6,000,000,000 nuclear base-pairs in a diploid cell <ref>Capelli et. al</ref>. For this reason it is obvious that hOGG1 must have an efficient mechanism to discriminate between GO and G even though they differ at the C8 and N7 (the paper). hOGG1 is able to discriminate GO from G with the help of a single hydrogen bond between a <scene name='Sandbox_164/Scene_4/1'>main chain carbonyl O of G42 and the protonated N7 position of the GO</scene> <ref> Structure Vol.13, 87-98</ref>. Additional structural studies have indicated that the GO is extruded from the DNA helix and inserted deeply into a <scene name='Sandbox_164/Scene_5/1'>catalytic pocket</scene> catalytic pocket where residues lining the pocket can directly interact to excise the lesion (7,the paper). The AP lyase activity uses a conserved lysine residue as a nucleophile to generate a covalently linked enzyme-DNA adduct, which undergoes a series of subsequent transformation resulting in DNA strand exscission on the 3’ side of the lesion. <br /> <br /> =References=<br /> <references/></div>

Riley Hicks