https://proteopedia.org/api.php?action=feedcontributions&feedformat=atom&user=Sam+HayesProteopedia - User contributions [en]2026-09-15T23:31:48ZUser contributionsMediaWiki 1.43.8https://proteopedia.org/index.php?title=Cas9_Sandbox&diff=2602649Cas9 Sandbox2016-05-25T18:35:48Z<p>Sam Hayes: </p>
<hr />
<div>== Function ==<br />
<StructureSection load='4un3' size='350' frame='true' side='right' caption='4un3 of Streptococcus pyogenes' scene='Insert optional scene name here' ><br />
[[Cas9]] is the RNA-guided [[DNA endonuclease]] used by the CRISPR (clustered regularly interspaced short palindromic repeats)-associated systems to generate double-strand DNA breaks in the invading DNA during an adaptive bacterial immune response. Three different types of CRISPR mechanisms have been discovered, however, only type II CRISPR systems are heavily researched. In vivo, [[Cas9]] requires CRISPR RNA (crRNA) and trans-activating crRNA (tracrRNA) to guide the endonuclease toward invading DNA based on the complementary sequence recognition of these RNAs. Cas9 then targets and cleaves foreign DNA to interfere with viral replication and integration into the host's genome. The CRISPR-associated endonuclease <scene name='71/714945/Pam_interaction/11'>Cas9</scene> has been exploited for use in genome editing systems. In such systems, an engineered single-guide RNA (sgRNA) is used to perform the function of crRNA-tracRNA complex to target double-stranded breaks in genomic DNA. Depending on what repair pathway is triggered, often dictated by the inclusion of additional engineered components, the targeted site either is disrupted or incorporates additional genetic sequences. <ref>PMID:24906146</ref><br />
<br />
<br />
== Structural highlights ==<br />
<br />
Cas9 is a structurally bilobed, containing specific domains for the recognition of target DNA and nucleases to cleave DNA strands. Each of these lobes contain three major units essential for a functional endonuclease, these are the essential <scene name='71/714945/Lobes_domain_of_cas9/5'>domains</scene>. <br />
<br />
The recognition lobe (REC) contains a long bridge helix, the REC-1 domain and the REC-2 domain. It is also the least conserved lobe through the types of Cas9. The long <scene name='71/714945/Alpha_helix_bridge/1'>α-helix bridge</scene>, which is arginine-rich, is essential for recognizing single guide RNA-DNA complexes on target DNA. This structure has been shown to be conserved through Cas9 proteins. The <scene name='71/714945/Rec-1_domain/2'>REC-1</scene> domain contains 25 α-helixes and two β-sheets, and is crucial to the function of Cas9 by recognizing a specific motif termed the repeat:anti-repeat region of the single guide RNA and DNA complex. The <scene name='71/714945/Rec-2_domain/1'>REC-2</scene> domain contains six α-helix’s in a bundle but there is no current understanding of its function.<br />
<br />
The nuclease lobe (NUC) contains a RuvC domain, HNH domain and the PAM-interacting domain (PI). The RuvC domain is comprised of three RuvC motifs that are made up of two-stranded antiparallel β-sheets, and six-stranded β-sheets, which are flanked by nine α-helices. The <scene name='71/714945/Ruvc_domain/1'>RuvC nuclease</scene> cleaves the non-complementary, single stranded DNA. This nuclease is active through the use of four catalytic residues shown in the previous scene. The <scene name='71/714945/Hnh_domain/3'>HNH domain</scene> is composed of a two-stranded antiparallel β-sheet which is flanked by four α-helixes and cleaves the complementary strand of target DNA. The four catalytic residues of this nuclease domain are highlighted in red. The <scene name='71/714945/Pi/1'>PI</scene> is made up of seven α-helixes and numerous strand-varying antiparallel β-sheets which recognize the PAM sequence on the non-complementary target DNA strand.<ref>PMID:24529477</ref><br />
<br />
<br />
== DNA Interaction ==<br />
Target DNA contains a protospacer adjacent motif on the non-complementary strand, which constitues the <scene name='71/714945/Pam_interaction/12'>Cas9 interaction at the PAM sequence</scene>. This canonical sequence of 5’-NGG-3’ is recognized by Cas9 and is essential for genetic interference and editing, therefore, it will not cleave the target sequence if the PAM sequence is absent. The double Guanine of the non-complementary sequence strand interacts via hydrogen bonding from the major groove through two conserved arginine residues on the carboxy-terminus of Cas9 <ref>PMID:25079318</ref>. The minor groove of the PAM sequence interacts with a serine, through a hydrogen bridge to the last guanine, and lysine residue on the complementary target strand of the middle guanine. <br />
<br />
The deoxyribose-phosphate backbone of the non-complementary strand is arranged in close proximity to various hydrogen bonding atoms, some of which are accomplished through water molecules, and ionic interactions. A phosphate lock loop provides local strand separation upstream of the PAM sequence when a Lysine and Serine residue stabilize target DNA. The PAM sequence recognition of Cas9 is an integral function of its specific binding, subsequent base pair melting and cleavage of target DNA.<br />
<br />
<br />
<br />
[[Image:Layout for schematic and structure with structure.png|660px]]<br />
[[Image:4un3 labeled.png|right|390px]]<br />
<br />
==Limitations==<br />
Despite the many advantages of CRISPR/Cas9 it still has two major limitations. The first is that CRISPR/Cas9 requires the presence of an NGG PAM. NGG PAM occurs approximately every 8bp causing it CRISPR/Cas9 to have less target sequence density than TALENS. This lower precision compared to TALENS may lead to CRISPR/Cas9 being used less in cases where a DSB needs to be targeted in smaller sequences. The next limitation is the use of DSBs. If cleavage occurs at an off-target site the genome can experience unexpected perturbations. As CRISPR/Cas9 and other genome editing methods move to a more clinical use these perturbations could increase the risk of developing tumors.<ref>PMID: 27218233</ref><br />
<br />
==Medicinal Applications==<br />
The CRISPR/Cas9 system has shown efficiency in treating viral infections that alter the host organisms' genome. HIV-1 is an example of a virus that may reside in an individual in a dormant state called a latent reservoir. <ref> PMID: 23974631 </ref> In this state, the viral DNA is not being transcribed into RNA, and the effects of the infection are nonexistent; however, the virus may begin transcribing its DNA at any time which would lead to the symptoms of HIV infection. The CRISPr/Cas9 system was successful at eradicating the HIV-1 virus from the infected individual, and also cleaving the viral DNA out of the hosts' genome, thus not allowing for later infection. <br />
<br />
==Ethical Controversy==<br />
<br />
The use of the Crispr/Cas9 has undergone much scrutiny. Those who are opposed to the use of Cas9 in the Crispr system for genome editing claim that the technology will ultimately lead to "designer babies," and we shouldn't alter the genomes of future generations without their consent. The National Institutes of Health has stated that they will not fund any gene-editing technologies for use on human embryos. <br />
<br />
<br />
<br />
== References ==<br />
<references/><br />
<br />
[[Category: Crispr]]<br />
[[Category: Crispr-associated]]<br />
[[Category: endonuclease]]<br />
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<br />
==3D structures of Cas9==<br />
<br />
===''Streptococcus pyogenes'' Cas9===<br />
<br />
* [[4un3]], [[4un4]], and [[4un5]] - ''S. pyogenes'' Cas9 bound to sgRNA and target DNA<br />
* [[4oo8]] - ''S. pyogenes'' Cas9 bound to sgRNA and target DNA<br />
* [[4cmp]]<br />
* [[4cmq]] - Mn<sup>2+</sup>-bound ''S. pyogenes'' Cas9<br />
<br />
=== ''Actinomyces naeslundii'' Cas9=== <br />
*[[4oge]]<br />
*[[4ogc]] - Mn<sup>2+</sup>-bound ''A.s naeslundii'' Cas9<br />
<br />
==See Also==<br />
[[HNH endonuclease]] <br/></div>Sam Hayeshttps://proteopedia.org/index.php?title=Cas9_Sandbox&diff=2602643Cas9 Sandbox2016-05-25T17:59:03Z<p>Sam Hayes: </p>
<hr />
<div>== Function ==<br />
<StructureSection load='4un3' size='350' frame='true' side='right' caption='4un3 of Streptococcus pyogenes' scene='Insert optional scene name here' ><br />
[[Cas9]] is the RNA-guided [[DNA endonuclease]] used by the CRISPR (clustered regularly interspaced short palindromic repeats)-associated systems to generate double-strand DNA breaks in the invading DNA during an adaptive bacterial immune response. Three different types of CRISPR mechanisms have been discovered, however, only type II CRISPR systems are heavily researched. In vivo, [[Cas9]] requires CRISPR RNA (crRNA) and trans-activating crRNA (tracrRNA) to guide the endonuclease toward invading DNA based on the complementary sequence recognition of these RNAs. Cas9 then targets and cleaves foreign DNA to interfere with viral replication. The CRISPR-associated endonuclease <scene name='71/714945/Pam_interaction/11'>Cas9</scene> has been exploited for use in genome editing systems. In such systems, an engineered single-guide RNA (sgRNA) is used to perform the function of crRNA-tracRNA complex to target double-stranded breaks in genomic DNA. Depending on what repair pathway is triggered, often dictated by the inclusion of additional engineered components, the targeted site either is disrupted or incorporates additional genetic sequences. <ref>PMID:24906146</ref><br />
<br />
<br />
== Structural highlights ==<br />
<br />
Cas9 is a structurally bilobed, containing specific domains for the recognition of target DNA and nucleases to cleave DNA strands. Each of these lobes contain three major units essential for a functional endonuclease, these are the essential <scene name='71/714945/Lobes_domain_of_cas9/5'>domains</scene>. <br />
<br />
The recognition lobe (REC) contains a long bridge helix, the REC-1 domain and the REC-2 domain. It is also the least conserved lobe through the types of Cas9. The long <scene name='71/714945/Alpha_helix_bridge/1'>α-helix bridge</scene>, which is arginine-rich, is essential for recognizing single guide RNA-DNA complexes on target DNA. This structure has been shown to be conserved through Cas9 proteins. The <scene name='71/714945/Rec-1_domain/2'>REC-1</scene> domain contains 25 α-helixes and two β-sheets, and is crucial to the function of Cas9 by recognizing a specific motif termed the repeat:anti-repeat region of the single guide RNA and DNA complex. The <scene name='71/714945/Rec-2_domain/1'>REC-2</scene> domain contains six α-helix’s in a bundle but there is no current understanding of its function.<br />
<br />
The nuclease lobe (NUC) contains a RuvC domain, HNH domain and the PAM-interacting domain (PI). The RuvC domain is comprised of three RuvC motifs that are made up of two-stranded antiparallel β-sheets, and six-stranded β-sheets, which are flanked by nine α-helices. The <scene name='71/714945/Ruvc_domain/1'>RuvC nuclease</scene> cleaves the non-complementary, single stranded DNA. This nuclease is active through the use of four catalytic residues shown in the previous scene. The <scene name='71/714945/Hnh_domain/3'>HNH domain</scene> is composed of a two-stranded antiparallel β-sheet which is flanked by four α-helixes and cleaves the complementary strand of target DNA. The four catalytic residues of this nuclease domain are highlighted in red. The <scene name='71/714945/Pi/1'>PI</scene> is made up of seven α-helixes and numerous strand-varying antiparallel β-sheets which recognize the PAM sequence on the non-complementary target DNA strand.<ref>PMID:24529477</ref><br />
<br />
<br />
== DNA Interaction ==<br />
Target DNA contains a protospacer adjacent motif on the non-complementary strand, which constitues the <scene name='71/714945/Pam_interaction/12'>Cas9 interaction at the PAM sequence</scene>. This canonical sequence of 5’-NGG-3’ is recognized by Cas9 and is essential for genetic interference and editing, therefore, it will not cleave the target sequence if the PAM sequence is absent. The double Guanine of the non-complementary sequence strand interacts via hydrogen bonding from the major groove through two conserved arginine residues on the carboxy-terminus of Cas9 <ref>PMID:25079318</ref>. The minor groove of the PAM sequence interacts with a serine, through a hydrogen bridge to the last guanine, and lysine residue on the complementary target strand of the middle guanine. <br />
<br />
The deoxyribose-phosphate backbone of the non-complementary strand is arranged in close proximity to various hydrogen bonding atoms, some of which are accomplished through water molecules, and ionic interactions. A phosphate lock loop provides local strand separation upstream of the PAM sequence when a Lysine and Serine residue stabilize target DNA. The PAM sequence recognition of Cas9 is an integral function of its specific binding, subsequent base pair melting and cleavage of target DNA.<br />
<br />
<br />
<br />
[[Image:Layout for schematic and structure with structure.png|660px]]<br />
[[Image:4un3 labeled.png|right|390px]]<br />
<br />
==Medicinal Applications==<br />
The CRISPR/Cas9 system has shown efficiency in treating viral infections that alter the host organisms' genome. HIV-1 is an example of a virus that may reside in an individual in a dormant state called a latent reservoir. <ref> PMID: 23974631 </ref> In this state, the viral DNA is not being transcribed into RNA, and the effects of the infection are nonexistent; however, the virus may begin transcribing its DNA at any time which would lead to the symptoms of HIV infection. The CRISPr/Cas9 system was successful at eradicating the HIV-1 virus from the infected individual, and also cleaving the viral DNA out of the hosts' genome, thus not allowing for later infection. <br />
<br />
==Ethical Controversy==<br />
<br />
The use of the Crispr/Cas9 has undergone much scrutiny. Those who are opposed to the use of Cas9 in the Crispr system for genome editing claim that the technology will ultimately lead to "designer babies," and we shouldn't alter the genomes of future generations without their consent. The National Institutes of Health has stated that they will not fund any gene-editing technologies for use on human embryos. <br />
<br />
<br />
<br />
== References ==<br />
<references/><br />
<br />
[[Category: Crispr]]<br />
[[Category: Crispr-associated]]<br />
[[Category: endonuclease]]<br />
<br />
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<br />
==3D structures of Cas9==<br />
<br />
===''Streptococcus pyogenes'' Cas9===<br />
<br />
* [[4un3]], [[4un4]], and [[4un5]] - ''S. pyogenes'' Cas9 bound to sgRNA and target DNA<br />
* [[4oo8]] - ''S. pyogenes'' Cas9 bound to sgRNA and target DNA<br />
* [[4cmp]]<br />
* [[4cmq]] - Mn<sup>2+</sup>-bound ''S. pyogenes'' Cas9<br />
<br />
=== ''Actinomyces naeslundii'' Cas9=== <br />
*[[4oge]]<br />
*[[4ogc]] - Mn<sup>2+</sup>-bound ''A.s naeslundii'' Cas9<br />
<br />
==See Also==<br />
[[HNH endonuclease]] <br/></div>Sam Hayeshttps://proteopedia.org/index.php?title=Cas9_Sandbox&diff=2602642Cas9 Sandbox2016-05-25T17:56:12Z<p>Sam Hayes: </p>
<hr />
<div>== Function ==<br />
<StructureSection load='4un3' size='350' frame='true' side='right' caption='4un3 of Streptococcus pyogenes' scene='Insert optional scene name here' ><br />
[[Cas9]] is the RNA-guided [[DNA endonuclease]] used by the CRISPR (clustered regularly interspaced short palindromic repeats)-associated systems to generate double-strand DNA breaks in the invading DNA during an adaptive bacterial immune response. Three different types of CRISPR mechanisms have been discovered, however, only type II CRISPR systems are heavily researched. In vivo, [[Cas9]] requires CRISPR RNA (crRNA) and trans-activating crRNA (tracrRNA) to guide the endonuclease toward invading DNA based on the complementary sequence recognition of these RNAs. Cas9 then targets and cleaves foreign DNA to interfere with viral replication. The CRISPR-associated endonuclease <scene name='71/714945/Pam_interaction/11'>Cas9</scene> has been exploited for use in genome editing systems. In such systems, an engineered single-guide RNA (sgRNA) is used to perform the function of crRNA-tracRNA complex to target double-stranded breaks in genomic DNA. Depending on what repair pathway is triggered, often dictated by the inclusion of additional engineered components, the targeted site either is disrupted or incorporates additional genetic sequences. <ref>PMID:24906146</ref><br />
<br />
<br />
== Structural highlights ==<br />
<br />
Cas9 is a structurally bilobed, containing specific domains for the recognition of target DNA and nucleases to cleave DNA strands. Each of these lobes contain three major units essential for a functional endonuclease, these are the essential <scene name='71/714945/Lobes_domain_of_cas9/5'>domains</scene>. <br />
<br />
The recognition lobe (REC) contains a long bridge helix, the REC-1 domain and the REC-2 domain. It is also the least conserved lobe through the types of Cas9. The long <scene name='71/714945/Alpha_helix_bridge/1'>α-helix bridge</scene>, which is arginine-rich, is essential for recognizing single guide RNA-DNA complexes on target DNA. This structure has been shown to be conserved through Cas9 proteins. The <scene name='71/714945/Rec-1_domain/2'>REC-1</scene> domain contains 25 α-helixes and two β-sheets, and is crucial to the function of Cas9 by recognizing a specific motif termed the repeat:anti-repeat region of the single guide RNA and DNA complex. The <scene name='71/714945/Rec-2_domain/1'>REC-2</scene> domain contains six α-helix’s in a bundle but there is no current understanding of its function.<br />
<br />
The nuclease lobe (NUC) contains a RuvC domain, HNH domain and the PAM-interacting domain (PI). The RuvC domain is comprised of three RuvC motifs that are made up of two-stranded antiparallel β-sheets, and six-stranded β-sheets, which are flanked by nine α-helices. The <scene name='71/714945/Ruvc_domain/1'>RuvC nuclease</scene> cleaves the non-complementary, single stranded DNA. This nuclease is active through the use of four catalytic residues shown in the previous scene. The <scene name='71/714945/Hnh_domain/3'>HNH domain</scene> is composed of a two-stranded antiparallel β-sheet which is flanked by four α-helixes and cleaves the complementary strand of target DNA. The four catalytic residues of this nuclease domain are highlighted in red. The <scene name='71/714945/Pi/1'>PI</scene> is made up of seven α-helixes and numerous strand-varying antiparallel β-sheets which recognize the PAM sequence on the non-complementary target DNA strand.<ref>PMID:24529477</ref><br />
<br />
<br />
== DNA Interaction ==<br />
Target DNA contains a protospacer adjacent motif on the non-complementary strand, which constitues the <scene name='71/714945/Pam_interaction/12'>Cas9 interaction at the PAM sequence</scene>. This canonical sequence of 5’-NGG-3’ is recognized by Cas9 and is essential for genetic interference and editing, therefore, it will not cleave the target sequence if the PAM sequence is absent. The double Guanine of the non-complementary sequence strand interacts via hydrogen bonding from the major groove through two conserved arginine residues on the carboxy-terminus of Cas9 <ref>PMID:25079318</ref>. The minor groove of the PAM sequence interacts with a serine, through a hydrogen bridge to the last guanine, and lysine residue on the complementary target strand of the middle guanine. <br />
<br />
The deoxyribose-phosphate backbone of the non-complementary strand is arranged in close proximity to various hydrogen bonding atoms, some of which are accomplished through water molecules, and ionic interactions. A phosphate lock loop provides local strand separation upstream of the PAM sequence when a Lysine and Serine residue stabilize target DNA. The PAM sequence recognition of Cas9 is an integral function of its specific binding, subsequent base pair melting and cleavage of target DNA.<br />
<br />
<br />
<br />
[[Image:Layout for schematic and structure with structure.png|660px]]<br />
[[Image:4un3 labeled.png|right|390px]]<br />
<br />
==Medicinal Applications==<br />
The CRISPR/Cas9 system has shown efficiency in treating viral infections that alter the host organisms' genome. HIV-1 is an example of a virus that may reside in an individual in a dormant state called a latent reservoir. <ref> PMID: 23974631 <ref/> In this state, the viral DNA is not being transcribed into RNA, and the effects of the infection are nonexistent; however, the virus may begin transcribing its DNA at any time which would lead to the symptoms of HIV infection. The CRISPr/Cas9 system was successful at eradicating the HIV-1 virus from the infected individual, and also cleaving the viral DNA out of the hosts' genome, thus not allowing for later infection. <br />
<br />
==Ethical Controversy==<br />
<br />
The use of the Crispr/Cas9 has undergone much scrutiny. Those who are opposed to the use of Cas9 in the Crispr system for genome editing claim that the technology will ultimately lead to "designer babies," and we shouldn't alter the genomes of future generations without their consent. The National Institutes of Health has stated that they will not fund any gene-editing technologies for use on human embryos. <br />
<br />
<br />
<br />
== References ==<br />
<references/><br />
<br />
[[Category: Crispr]]<br />
[[Category: Crispr-associated]]<br />
[[Category: endonuclease]]<br />
<br />
<br />
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<br />
<br />
==3D structures of Cas9==<br />
<br />
===''Streptococcus pyogenes'' Cas9===<br />
<br />
* [[4un3]], [[4un4]], and [[4un5]] - ''S. pyogenes'' Cas9 bound to sgRNA and target DNA<br />
* [[4oo8]] - ''S. pyogenes'' Cas9 bound to sgRNA and target DNA<br />
* [[4cmp]]<br />
* [[4cmq]] - Mn<sup>2+</sup>-bound ''S. pyogenes'' Cas9<br />
<br />
=== ''Actinomyces naeslundii'' Cas9=== <br />
*[[4oge]]<br />
*[[4ogc]] - Mn<sup>2+</sup>-bound ''A.s naeslundii'' Cas9<br />
<br />
==See Also==<br />
[[HNH endonuclease]] <br/></div>Sam Hayeshttps://proteopedia.org/index.php?title=Cas9_Sandbox&diff=2602641Cas9 Sandbox2016-05-25T17:54:46Z<p>Sam Hayes: </p>
<hr />
<div>== Function ==<br />
<StructureSection load='4un3' size='350' frame='true' side='right' caption='4un3 of Streptococcus pyogenes' scene='Insert optional scene name here' ><br />
[[Cas9]] is the RNA-guided [[DNA endonuclease]] used by the CRISPR (clustered regularly interspaced short palindromic repeats)-associated systems to generate double-strand DNA breaks in the invading DNA during an adaptive bacterial immune response. Three different types of CRISPR mechanisms have been discovered, however, only type II CRISPR systems are heavily researched. In vivo, [[Cas9]] requires CRISPR RNA (crRNA) and trans-activating crRNA (tracrRNA) to guide the endonuclease toward invading DNA based on the complementary sequence recognition of these RNAs. Cas9 then targets and cleaves foreign DNA to interfere with viral replication. The CRISPR-associated endonuclease <scene name='71/714945/Pam_interaction/11'>Cas9</scene> has been exploited for use in genome editing systems. In such systems, an engineered single-guide RNA (sgRNA) is used to perform the function of crRNA-tracRNA complex to target double-stranded breaks in genomic DNA. Depending on what repair pathway is triggered, often dictated by the inclusion of additional engineered components, the targeted site either is disrupted or incorporates additional genetic sequences. <ref>PMID:24906146</ref><br />
<br />
<br />
== Structural highlights ==<br />
<br />
Cas9 is a structurally bilobed, containing specific domains for the recognition of target DNA and nucleases to cleave DNA strands. Each of these lobes contain three major units essential for a functional endonuclease, these are the essential <scene name='71/714945/Lobes_domain_of_cas9/5'>domains</scene>. <br />
<br />
The recognition lobe (REC) contains a long bridge helix, the REC-1 domain and the REC-2 domain. It is also the least conserved lobe through the types of Cas9. The long <scene name='71/714945/Alpha_helix_bridge/1'>α-helix bridge</scene>, which is arginine-rich, is essential for recognizing single guide RNA-DNA complexes on target DNA. This structure has been shown to be conserved through Cas9 proteins. The <scene name='71/714945/Rec-1_domain/2'>REC-1</scene> domain contains 25 α-helixes and two β-sheets, and is crucial to the function of Cas9 by recognizing a specific motif termed the repeat:anti-repeat region of the single guide RNA and DNA complex. The <scene name='71/714945/Rec-2_domain/1'>REC-2</scene> domain contains six α-helix’s in a bundle but there is no current understanding of its function.<br />
<br />
The nuclease lobe (NUC) contains a RuvC domain, HNH domain and the PAM-interacting domain (PI). The RuvC domain is comprised of three RuvC motifs that are made up of two-stranded antiparallel β-sheets, and six-stranded β-sheets, which are flanked by nine α-helices. The <scene name='71/714945/Ruvc_domain/1'>RuvC nuclease</scene> cleaves the non-complementary, single stranded DNA. This nuclease is active through the use of four catalytic residues shown in the previous scene. The <scene name='71/714945/Hnh_domain/3'>HNH domain</scene> is composed of a two-stranded antiparallel β-sheet which is flanked by four α-helixes and cleaves the complementary strand of target DNA. The four catalytic residues of this nuclease domain are highlighted in red. The <scene name='71/714945/Pi/1'>PI</scene> is made up of seven α-helixes and numerous strand-varying antiparallel β-sheets which recognize the PAM sequence on the non-complementary target DNA strand.<ref>PMID:24529477</ref><br />
<br />
<br />
== DNA Interaction ==<br />
Target DNA contains a protospacer adjacent motif on the non-complementary strand, which constitues the <scene name='71/714945/Pam_interaction/12'>Cas9 interaction at the PAM sequence</scene>. This canonical sequence of 5’-NGG-3’ is recognized by Cas9 and is essential for genetic interference and editing, therefore, it will not cleave the target sequence if the PAM sequence is absent. The double Guanine of the non-complementary sequence strand interacts via hydrogen bonding from the major groove through two conserved arginine residues on the carboxy-terminus of Cas9 <ref>PMID:25079318</ref>. The minor groove of the PAM sequence interacts with a serine, through a hydrogen bridge to the last guanine, and lysine residue on the complementary target strand of the middle guanine. <br />
<br />
The deoxyribose-phosphate backbone of the non-complementary strand is arranged in close proximity to various hydrogen bonding atoms, some of which are accomplished through water molecules, and ionic interactions. A phosphate lock loop provides local strand separation upstream of the PAM sequence when a Lysine and Serine residue stabilize target DNA. The PAM sequence recognition of Cas9 is an integral function of its specific binding, subsequent base pair melting and cleavage of target DNA.<br />
<br />
<br />
<br />
[[Image:Layout for schematic and structure with structure.png|660px]]<br />
[[Image:4un3 labeled.png|right|390px]]<br />
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<br />
==3D structures of Cas9==<br />
<br />
===''Streptococcus pyogenes'' Cas9===<br />
<br />
* [[4un3]], [[4un4]], and [[4un5]] - ''S. pyogenes'' Cas9 bound to sgRNA and target DNA<br />
* [[4oo8]] - ''S. pyogenes'' Cas9 bound to sgRNA and target DNA<br />
* [[4cmp]]<br />
* [[4cmq]] - Mn<sup>2+</sup>-bound ''S. pyogenes'' Cas9<br />
<br />
=== ''Actinomyces naeslundii'' Cas9=== <br />
*[[4oge]]<br />
*[[4ogc]] - Mn<sup>2+</sup>-bound ''A.s naeslundii'' Cas9<br />
<br />
==See Also==<br />
[[HNH endonuclease]] <br/><br />
<br />
==Medicinal Applications==<br />
The CRISPR/Cas9 system has shown efficiency in treating viral infections that alter the host organisms' genome. HIV-1 is an example of a virus that may reside in an individual in a dormant state called a latent reservoir. <ref> PMID: 23974631 <ref/> In this state, the viral DNA is not being transcribed into RNA, and the effects of the infection are nonexistent; however, the virus may begin transcribing its DNA at any time which would lead to the symptoms of HIV infection. The CRISPr/Cas9 system was successful at eradicating the HIV-1 virus from the infected individual, and also cleaving the viral DNA out of the hosts' genome, thus not allowing for later infection. <br />
<br />
==Ethical Controversy==<br />
<br />
The use of the Crispr/Cas9 has undergone much scrutiny. Those who are opposed to the use of Cas9 in the Crispr system for genome editing claim that the technology will ultimately lead to "designer babies," and we shouldn't alter the genomes of future generations without their consent. The National Institutes of Health has stated that they will not fund any gene-editing technologies for use on human embryos. <br />
<br />
<br />
<br />
== References ==<br />
<references/><br />
<br />
[[Category: Crispr]]<br />
[[Category: Crispr-associated]]<br />
[[Category: endonuclease]]</div>Sam Hayeshttps://proteopedia.org/index.php?title=Cas9_Sandbox&diff=2602640Cas9 Sandbox2016-05-25T17:53:47Z<p>Sam Hayes: </p>
<hr />
<div>== Function ==<br />
<StructureSection load='4un3' size='350' frame='true' side='right' caption='4un3 of Streptococcus pyogenes' scene='Insert optional scene name here' ><br />
[[Cas9]] is the RNA-guided [[DNA endonuclease]] used by the CRISPR (clustered regularly interspaced short palindromic repeats)-associated systems to generate double-strand DNA breaks in the invading DNA during an adaptive bacterial immune response. Three different types of CRISPR mechanisms have been discovered, however, only type II CRISPR systems are heavily researched. In vivo, [[Cas9]] requires CRISPR RNA (crRNA) and trans-activating crRNA (tracrRNA) to guide the endonuclease toward invading DNA based on the complementary sequence recognition of these RNAs. Cas9 then targets and cleaves foreign DNA to interfere with viral replication. The CRISPR-associated endonuclease <scene name='71/714945/Pam_interaction/11'>Cas9</scene> has been exploited for use in genome editing systems. In such systems, an engineered single-guide RNA (sgRNA) is used to perform the function of crRNA-tracRNA complex to target double-stranded breaks in genomic DNA. Depending on what repair pathway is triggered, often dictated by the inclusion of additional engineered components, the targeted site either is disrupted or incorporates additional genetic sequences. <ref>PMID:24906146</ref><br />
<br />
<br />
== Structural highlights ==<br />
<br />
Cas9 is a structurally bilobed, containing specific domains for the recognition of target DNA and nucleases to cleave DNA strands. Each of these lobes contain three major units essential for a functional endonuclease, these are the essential <scene name='71/714945/Lobes_domain_of_cas9/5'>domains</scene>. <br />
<br />
The recognition lobe (REC) contains a long bridge helix, the REC-1 domain and the REC-2 domain. It is also the least conserved lobe through the types of Cas9. The long <scene name='71/714945/Alpha_helix_bridge/1'>α-helix bridge</scene>, which is arginine-rich, is essential for recognizing single guide RNA-DNA complexes on target DNA. This structure has been shown to be conserved through Cas9 proteins. The <scene name='71/714945/Rec-1_domain/2'>REC-1</scene> domain contains 25 α-helixes and two β-sheets, and is crucial to the function of Cas9 by recognizing a specific motif termed the repeat:anti-repeat region of the single guide RNA and DNA complex. The <scene name='71/714945/Rec-2_domain/1'>REC-2</scene> domain contains six α-helix’s in a bundle but there is no current understanding of its function.<br />
<br />
The nuclease lobe (NUC) contains a RuvC domain, HNH domain and the PAM-interacting domain (PI). The RuvC domain is comprised of three RuvC motifs that are made up of two-stranded antiparallel β-sheets, and six-stranded β-sheets, which are flanked by nine α-helices. The <scene name='71/714945/Ruvc_domain/1'>RuvC nuclease</scene> cleaves the non-complementary, single stranded DNA. This nuclease is active through the use of four catalytic residues shown in the previous scene. The <scene name='71/714945/Hnh_domain/3'>HNH domain</scene> is composed of a two-stranded antiparallel β-sheet which is flanked by four α-helixes and cleaves the complementary strand of target DNA. The four catalytic residues of this nuclease domain are highlighted in red. The <scene name='71/714945/Pi/1'>PI</scene> is made up of seven α-helixes and numerous strand-varying antiparallel β-sheets which recognize the PAM sequence on the non-complementary target DNA strand.<ref>PMID:24529477</ref><br />
<br />
<br />
== DNA Interaction ==<br />
Target DNA contains a protospacer adjacent motif on the non-complementary strand, which constitues the <scene name='71/714945/Pam_interaction/12'>Cas9 interaction at the PAM sequence</scene>. This canonical sequence of 5’-NGG-3’ is recognized by Cas9 and is essential for genetic interference and editing, therefore, it will not cleave the target sequence if the PAM sequence is absent. The double Guanine of the non-complementary sequence strand interacts via hydrogen bonding from the major groove through two conserved arginine residues on the carboxy-terminus of Cas9 <ref>PMID:25079318</ref>. The minor groove of the PAM sequence interacts with a serine, through a hydrogen bridge to the last guanine, and lysine residue on the complementary target strand of the middle guanine. <br />
<br />
The deoxyribose-phosphate backbone of the non-complementary strand is arranged in close proximity to various hydrogen bonding atoms, some of which are accomplished through water molecules, and ionic interactions. A phosphate lock loop provides local strand separation upstream of the PAM sequence when a Lysine and Serine residue stabilize target DNA. The PAM sequence recognition of Cas9 is an integral function of its specific binding, subsequent base pair melting and cleavage of target DNA.<br />
<br />
<br />
<br />
[[Image:Layout for schematic and structure with structure.png|660px]]<br />
[[Image:4un3 labeled.png|right|390px]]<br />
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<br />
<br />
<br />
<br />
==3D structures of Cas9==<br />
<br />
===''Streptococcus pyogenes'' Cas9===<br />
<br />
* [[4un3]], [[4un4]], and [[4un5]] - ''S. pyogenes'' Cas9 bound to sgRNA and target DNA<br />
* [[4oo8]] - ''S. pyogenes'' Cas9 bound to sgRNA and target DNA<br />
* [[4cmp]]<br />
* [[4cmq]] - Mn<sup>2+</sup>-bound ''S. pyogenes'' Cas9<br />
<br />
=== ''Actinomyces naeslundii'' Cas9=== <br />
*[[4oge]]<br />
*[[4ogc]] - Mn<sup>2+</sup>-bound ''A.s naeslundii'' Cas9<br />
<br />
==See Also==<br />
[[HNH endonuclease]] <br/><br />
<br />
==Medicinal Applications==<br />
The CRISPR/Cas9 system has shown efficiency in treating viral infections that alter the host organisms' genome. HIV-1 is an example of a virus that may reside in an individual in a dormant state called a latent reservoir. <ref> PMID: 23974631 <ref/> In this state, the viral DNA is not being transcribed into RNA, and the effects of the infection are nonexistent; however, the virus may begin transcribing its DNA at any time which would lead to the symptoms of HIV infection. The CRISPr/Cas9 system was successful at eradicating the HIV-1 virus from the infected individual, and also cleaving the viral DNA out of the hosts' genome, thus not allowing for later infection. <br />
==Ethical Controversy==<br />
<br />
The use of the Crispr/Cas9 has undergone much scrutiny. Those who are opposed to the use of Cas9 in the Crispr system for genome editing claim that the technology will ultimately lead to "designer babies," and we shouldn't alter the genomes of future generations without their consent. The National Institutes of Health has stated that they will not fund any gene-editing technologies for use on human embryos. <br />
<br />
<br />
<br />
== References ==<br />
<references/><br />
<br />
[[Category: Crispr]]<br />
[[Category: Crispr-associated]]<br />
[[Category: endonuclease]]</div>Sam Hayeshttps://proteopedia.org/index.php?title=Cas9_Sandbox&diff=2602620Cas9 Sandbox2016-05-25T14:46:23Z<p>Sam Hayes: </p>
<hr />
<div>== Function ==<br />
<StructureSection load='4un3' size='350' frame='true' side='right' caption='4un3 of Streptococcus pyogenes' scene='Insert optional scene name here' ><br />
[[Cas9]] is the RNA-guided [[DNA endonuclease]] used by the CRISPR (clustered regularly interspaced short palindromic repeats)-associated systems to generate double-strand DNA breaks in the invading DNA during an adaptive bacterial immune response. Three different types of CRISPR mechanisms have been discovered, however, only type II CRISPR systems are heavily researched. In vivo, [[Cas9]] requires CRISPR RNA (crRNA) and trans-activating crRNA (tracrRNA) to guide the endonuclease toward invading DNA based on the complementary sequence recognition of these RNAs. Cas9 then targets and cleaves foreign DNA to interfere with viral replication. The CRISPR-associated endonuclease <scene name='71/714945/Pam_interaction/11'>Cas9</scene> has been exploited for use in genome editing systems. In such systems, an engineered single-guide RNA (sgRNA) is used to perform the function of crRNA-tracRNA complex to target double-stranded breaks in genomic DNA. Depending on what repair pathway is triggered, often dictated by the inclusion of additional engineered components, the targeted site either is disrupted or incorporates additional genetic sequences. <ref>PMID:24906146</ref><br />
<br />
<br />
== Structural highlights ==<br />
<br />
Cas9 is a structurally bilobed, containing specific domains for the recognition of target DNA and nucleases to cleave DNA strands. Each of these lobes contain three major units essential for a functional endonuclease, these are the essential <scene name='71/714945/Lobes_domain_of_cas9/5'>domains</scene>. <br />
<br />
The recognition lobe (REC) contains a long bridge helix, the REC-1 domain and the REC-2 domain. It is also the least conserved lobe through the types of Cas9. The long <scene name='71/714945/Alpha_helix_bridge/1'>α-helix bridge</scene>, which is arginine-rich, is essential for recognizing single guide RNA-DNA complexes on target DNA. This structure has been shown to be conserved through Cas9 proteins. The <scene name='71/714945/Rec-1_domain/2'>REC-1</scene> domain contains 25 α-helixes and two β-sheets, and is crucial to the function of Cas9 by recognizing a specific motif termed the repeat:anti-repeat region of the single guide RNA and DNA complex. The <scene name='71/714945/Rec-2_domain/1'>REC-2</scene> domain contains six α-helix’s in a bundle but there is no current understanding of its function.<br />
<br />
The nuclease lobe (NUC) contains a RuvC domain, HNH domain and the PAM-interacting domain (PI). The RuvC domain is comprised of three RuvC motifs that are made up of two-stranded antiparallel β-sheets, and six-stranded β-sheets, which are flanked by nine α-helices. The <scene name='71/714945/Ruvc_domain/1'>RuvC nuclease</scene> cleaves the non-complementary, single stranded DNA. This nuclease is active through the use of four catalytic residues shown in the previous scene. The <scene name='71/714945/Hnh_domain/3'>HNH domain</scene> is composed of a two-stranded antiparallel β-sheet which is flanked by four α-helixes and cleaves the complementary strand of target DNA. The four catalytic residues of this nuclease domain are highlighted in red. The <scene name='71/714945/Pi/1'>PI</scene> is made up of seven α-helixes and numerous strand-varying antiparallel β-sheets which recognize the PAM sequence on the non-complementary target DNA strand.<ref>PMID:24529477</ref><br />
<br />
<br />
== DNA Interaction ==<br />
Target DNA contains a protospacer adjacent motif on the non-complementary strand, which constitues the <scene name='71/714945/Pam_interaction/12'>Cas9 interaction at the PAM sequence</scene>. This canonical sequence of 5’-NGG-3’ is recognized by Cas9 and is essential for genetic interference and editing, therefore, it will not cleave the target sequence if the PAM sequence is absent. The double Guanine of the non-complementary sequence strand interacts via hydrogen bonding from the major groove through two conserved arginine residues on the carboxy-terminus of Cas9 <ref>PMID:25079318</ref>. The minor groove of the PAM sequence interacts with a serine, through a hydrogen bridge to the last guanine, and lysine residue on the complementary target strand of the middle guanine. <br />
<br />
The deoxyribose-phosphate backbone of the non-complementary strand is arranged in close proximity to various hydrogen bonding atoms, some of which are accomplished through water molecules, and ionic interactions. A phosphate lock loop provides local strand separation upstream of the PAM sequence when a Lysine and Serine residue stabilize target DNA. The PAM sequence recognition of Cas9 is an integral function of its specific binding, subsequent base pair melting and cleavage of target DNA.<br />
<br />
<br />
<br />
[[Image:Layout for schematic and structure with structure.png|660px]]<br />
[[Image:4un3 labeled.png|right|390px]]<br />
<br />
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<br />
<br />
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<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
==3D structures of Cas9==<br />
<br />
===''Streptococcus pyogenes'' Cas9===<br />
<br />
* [[4un3]], [[4un4]], and [[4un5]] - ''S. pyogenes'' Cas9 bound to sgRNA and target DNA<br />
* [[4oo8]] - ''S. pyogenes'' Cas9 bound to sgRNA and target DNA<br />
* [[4cmp]]<br />
* [[4cmq]] - Mn<sup>2+</sup>-bound ''S. pyogenes'' Cas9<br />
<br />
=== ''Actinomyces naeslundii'' Cas9=== <br />
*[[4oge]]<br />
*[[4ogc]] - Mn<sup>2+</sup>-bound ''A.s naeslundii'' Cas9<br />
<br />
==See Also==<br />
[[HNH endonuclease]] <br/><br />
<br />
==Ethical Controversy==<br />
<br />
The use of the Crispr/Cas9 has undergone much scrutiny. Those who are opposed to the use of Cas9 in the Crispr system for genome editing claim that the technology will ultimately lead to "designer babies," and we shouldn't alter the genomes of future generations without their consent. The National Institutes of Health has stated that they will not fund any gene-editing technologies for use on human embryos. <br />
<br />
<br />
<br />
== References ==<br />
<references/><br />
<br />
[[Category: Crispr]]<br />
[[Category: Crispr-associated]]<br />
[[Category: endonuclease]]</div>Sam Hayeshttps://proteopedia.org/index.php?title=Dicer&diff=2602583Dicer2016-05-23T18:07:24Z<p>Sam Hayes: </p>
<hr />
<div>==Dicer==<br />
<StructureSection load='4NH3' size='340' side='right' caption="Dicer' scene='4NH3_dimer/1'><br />
<br />
==Introduction==<br />
<br />
<StructureSection load='2EB1' size='400' side='right' caption='Human Endoribonuclease Dicer' scene=''><br />
<br />
</StructureSection><br />
<br />
==Introduction==<br />
<br />
Dicer is a type of [[Ribonuclease]] that processes potentially harmful double-stranded RNA (dsRNA) into microRNA and small-interfering RNA (siRNA) to be used in the process of RNA interference. Dicer is commonly utilized by cells in order to prevent the assimilation of viral DNA into the cells’ genome. The viral DNA is butchered into smaller segments that are each about 21 nucleotides long; the cut take places at the 5’ phosphate and the 3’ hydroxyl, and usually includes a 2 nucleotide overhang. There is a single processing center in HS Dicer implying that there are two catalytic sites which help form products with the 2 3' overhang. These newly formed segments attach themselves to single stranded mRNA which ultimately leads to mRNA degradation by the cell and translational suppression. The dicer enzyme in humans contains three domains: the <scene name='70/706244/Rnase_iii_1/1'>RNase III 1</scene>, <scene name='70/706244/Rnase_iii_2/1'>RNase III 2</scene>, and the <scene name='70/706244/Paz_domain/1'>Paz Domain</scene>.<ref>PMID: 16410517</ref> There are three classes of RNase III proteins which are divided into categories called Escherichia coli RNase III, <scene name='70/706244/Drosha/1'>Drosha</scene>, and Dicer which are given the numbers one, two, and three respectively. The Escherichia coli RNase III class has one domain while the Drosha and dicer have two domains each. There is no evidence of the first class of enzymes in mammals. <br />
<br />
Dicer, or endoribonuclease Dicer, was discovered/named in 2001 by Emily Bernstein. She was a graduate student in Greg Hannon's lab at the Cold Spring Harbor Laboratory in New York. She was trying to discover the enzyme that was responsible for removing small RNA fragments from double-stranded RNA. The dicer enzyme was found by isolating it from the RISC complex in the RNAi mechanism. It was known that RISC was not responsible for chopping up these small RNA fragments, so this complex was isolated from the system to locate the enzyme that was the source for these RNA fragments.<ref>PMID: 11201747</ref><br />
<br />
Dicer is a member of the RNase III family, is known as drosophilia CG4792 and it is found in multiple organisms.(2,3) The discovery of Dicer was important for understanding the regulation of gene expression and the epigenetic silencing of genes by miRNA. The human endoribonuclease Dicer is 219 kDa, which is larger than many other organisms' Dicer enzymes. This is due to Humans having different domains present, and in many cases, more domains.(3) <br />
<br />
==Structure==<br />
Human Dicer (hDicer) is a <scene name='70/706244/4nh3_dimer/1'>dimer</scene>. Each chain is a large multidomain enzyme whose C-terminal half includes a PAZ domain, a pair of tandem RNase III domains, and a double-stranded RNA-binding domain.<ref>PMID: 17920623</ref> There are four <scene name='70/706244/Mg_2eb1/1'>magnesium</scene> ions that bind to the hDicer RNase IIIb homodimer. There are oxygen ligands bonded to each Magnesium, which create an <scene name='70/706244/Mg_2eb1/3'>octahedral</scene> geometry on each Magnesium. The <scene name='70/706244/Mg_2eb1/5'>amino acids</scene> amino acids present on the oxygen ligands are Glutamic Acid and Aspartic Acid.<br />
<br />
Human Dicer is made up of helicase and PAZ domains in addition to two RNaseIII domains, A and B, and two double stranded RNA binding domains. The PAZ domain binds the 3' overhang of the dsRNA, while the two dsRNA binding domains bind to the dsRNA to hold the strand in place. At the same time, RNaseIIIa and RNaseIIIb form a dimer, and bind to the dsRNA via the active site. The active site is made up of a combination of the two RNaseIII domains. Both domains contain two Mg2+ ions which each stabilize two glutamine residues and two aspartic acid residues. <scene name='60/602707/Active_site/2'>Active Site</scene> These combine to form the two halves of the active site which allow the two RNaseIII domains to form the pseudo-dimer around the dsRNA. <scene name='60/602707/Trench/2'>pseudodimer</scene> Between the 3' end of the dsRNA which is bound to the PAZ domain, and the 5' end, which is bound to the PAZ domain loop. This allows for 25 nucleotides to be between the 3' binding site and the RNaseIIIa domain, which is then cleaved to form the RNA fragment. In this mechanism, the Dicer acts as a 25 nucleotide long ruler.(2)<br />
<br />
== Importance ==<br />
<br />
The Human Dicer and its mechanism is of the utmost importance because it cleaves these dsRNA's to form small interfering RNA or microRNA, which are then integrated into the RNA-induced silencing complex, or the RISC complex.(2,4) This complex then targets mRNA and prevents translation by disrupting the targeted gene. Without Dicer, gene silencing cannot occur. Therefore, without Dicer, DNA and RNA cannot be regulated.<br />
<br />
==Pathology==<br />
Mutations involving the dicer protein have been linked to the development of diseases in humans. Conditions such as pleuropulmonary blastoma<ref>PMID: 19556464</ref>, goiter multinodular<ref>PMID: 21205968</ref>, and rhabdomyosarcoma<ref>PMID: 21882293</ref> are related to dicer malfunction. Pleuropulmonary blastoma, goiter multinodular, cystic nephroma, and Sertoli-Leydig cell tumors are due a mutation in the Dicer1 gene given the name Dicer1 Syndrome. Dicer1 Syndrome is an inherited disorder that causes the risk of malignant tumors and benign tumors to increase. This occurs because short Dicer proteins are formed that cannot help in the production of miRNA, which can cause cells to grow into tumors. The risk of tumors is mainly increased in the lungs, kidneys, ovaries, and thyroid. Dicer1 Syndrome is transferred in an autosomal dominant pattern. The top treatment is surgery to remove the tumor.<br />
Dicer is known to be a direct cause of macular degeneration. The abscence of Dicer in retinal pigment epithelium causes the eye to break down into macular degeneration. It is hypothesized that Dicer has a specific role in maintaining this retinal health.(5)<br />
<br />
== References ==<br />
<references/><br />
1. Bernstein, E, Caudy, A, Hammond, S, and Hannon, G. (2001) Role for a Bidentate ribonuclease in the initial step of RNA interference. Cold Spring Harbor Laboratory. Nature, Vol 409, pgs. 363-367<br />
<br />
2. MacRae, I. (2006) Structural Basis for Double-Stranded RNA processing by Dicer. Science, Vol 311, pgs. 195-198<br />
<br />
3. Hammond, S. (2005) Dicing and Slicing: The Core machinery of the RNA interference pathway. University of North Carolina. Federation of European Biochemical Societies, Letters 579, pgs. 5822-5829<br />
<br />
4. Khaiwesh, B, Asif Arif, M, Seumel, G, Ossowski, S, Weigel, D, Reski, R, and Frank, W. (2010) Transcriptional control of gene expression by microRNAs. Cell, Vol 140, pgs. 111-122<br />
<br />
5. Lau, P, Potter, C, Carragher, B, MacRae, I. (2009) Structure of the Human dicer-TRBP complex by Electron Microscopy. Cell, October 14, 2009, pgs. 1326-1332.<br />
<references/></div>Sam Hayeshttps://proteopedia.org/index.php?title=Dicer&diff=2602569Dicer2016-05-23T15:42:01Z<p>Sam Hayes: </p>
<hr />
<div>==Dicer==<br />
<StructureSection load='4NH3' size='340' side='right' caption="Dicer' scene='4NH3_dimer/1'><br />
<br />
==Introduction==<br />
Dicer is a type of [[Ribonuclease]] that processes potentially harmful double-stranded RNA (dsRNA) into microRNA and small-interfering RNA (siRNA) to be used in the process of RNA interference. Dicer is commonly utilized by cells in order to prevent the assimilation of viral DNA into the cells’ genome. The viral DNA is butchered into smaller segments that are each about 21 nucleotides long; the cut take places at the 5’ phosphate and the 3’ hydroxyl, and usually includes a 2 nucleotide overhang. There is a single processing center in HS Dicer implying that there are two catalytic sites which help form products with the 2 3' overhang. These newly formed segments attach themselves to single stranded mRNA which ultimately leads to mRNA degradation by the cell and translational suppression. The dicer enzyme in humans contains three domains: the <scene name='70/706244/Rnase_iii_1/1'>RNase III 1</scene>, <scene name='70/706244/Rnase_iii_2/1'>RNase III 2</scene>, and the <scene name='70/706244/Paz_domain/1'>Paz Domain</scene>.<ref>PMID: 16410517</ref> There are three classes of RNase III proteins which are divided into categories called Escherichia coli RNase III, <scene name='70/706244/Drosha/1'>Drosha</scene>, and Dicer which are given the numbers one, two, and three respectively. The Escherichia coli RNase III class has one domain while the Drosha and dicer have two domains each. There is no evidence of the first class of enzymes in mammals. <br />
<br />
<br />
==Structure==<br />
Human Dicer (hDicer) is a <scene name='70/706244/4nh3_dimer/1'>dimer</scene>. Each chain is a large multidomain enzyme whose C-terminal half includes a PAZ domain, a pair of tandem RNase III domains, and a double-stranded RNA-binding domain.<ref>PMID: 17920623</ref> There are four <scene name='70/706244/Mg_2eb1/1'>magnesium</scene> ions that bind to the hDicer RNase IIIb homodimer. There are oxygen ligands bonded to each Magnesium, which create an <scene name='70/706244/Mg_2eb1/3'>octahedral</scene> geometry on each Magnesium. The <scene name='70/706244/Mg_2eb1/5'>amino acids</scene> amino acids present on the oxygen ligands are Glutamic Acid and Aspartic Acid.<br />
<br />
==Pathology==<br />
Mutations involving the dicer protein have been linked to the development of diseases in humans. Conditions such as pleuropulmonary blastoma<ref>PMID: 19556464</ref>, goiter multinodular<ref>PMID: 21205968</ref>, and rhabdomyosarcoma<ref>PMID: 21882293</ref> are related to dicer malfunction. <br />
<br />
== References ==<br />
<references/></div>Sam Hayeshttps://proteopedia.org/index.php?title=Dicer&diff=2602568Dicer2016-05-23T15:35:25Z<p>Sam Hayes: </p>
<hr />
<div>==Dicer==<br />
<StructureSection load='4NH3' size='340' side='right' caption="Dicer' scene='4NH3_dimer/1'><br />
<br />
==Introduction==<br />
Dicer is a type of [[Ribonuclease]] that processes potentially harmful double-stranded RNA (dsRNA) into microRNA and small-interfering RNA (siRNA) to be used in the process of RNA interference. Dicer is commonly utilized by cells in order to prevent the assimilation of viral DNA into the cells’ genome. The viral DNA is butchered into smaller segments that are each about 21 nucleotides long; the cut take places at the 5’ phosphate and the 3’ hydroxyl, and usually includes a 2 nucleotide overhang. There is a single processing center in HS Dicer implying that there are two catalytic sites which help form products with the 2 3' overhang. These newly formed segments attach themselves to single stranded mRNA which ultimately leads to mRNA degradation by the cell and translational suppression. The dicer enzyme in humans contains three domains: the <scene name='70/706244/Rnase_iii_1/1'>RNase III 1</scene>, <scene name='70/706244/Rnase_iii_2/1'>RNase III 2</scene>, and the <scene name='70/706244/Paz_domain/1'>Paz Domain</scene>.<ref>PMID: 16410517</ref> There are three classes of RNase III proteins which are divided into categories called Escherichia coli RNase III, <scene name='70/706244/Drosha/1'>Drosha</scene>, and Dicer which are given the numbers one, two, and three respectively. The Escherichia coli RNase III class has one domain while the Drosha and dicer have two domains each. There is no evidence of the first class of enzymes in mammals. <br />
<br />
<br />
==Structure==<br />
Human Dicer (hDicer) is a <scene name='70/706244/4nh3_dimer/1'>dimer</scene>. Each chain is a large multidomain enzyme whose C-terminal half includes a PAZ domain, a pair of tandem RNase III domains, and a double-stranded RNA-binding domain.<ref>PMID: 17920623</ref> There are four <scene name='70/706244/Mg_2eb1/1'>magnesium</scene> ions that bind to the hDicer RNase IIIb homodimer. There are oxygen ligands bonded to each Magnesium, which create an <scene name='70/706244/Mg_2eb1/3'>octahedral</scene> geometry on each Magnesium. The <scene name='70/706244/Mg_2eb1/5'>amino acids</scene> amino acids present on the oxygen ligands are Glutamic Acid and Aspartic Acid.<br />
<br />
==Pathology==<br />
Mutations involving the dicer protein have been linked to the development of diseases in humans. <br />
<br />
== References ==<br />
<references/></div>Sam Hayeshttps://proteopedia.org/index.php?title=Dicer&diff=2602567Dicer2016-05-23T15:34:43Z<p>Sam Hayes: </p>
<hr />
<div>==Introduction==<br />
<StructureSection load='4NH3' size='340' side='right' caption="Dicer' scene='4NH3_dimer/1'><br />
<br />
<br />
Dicer is a type of [[Ribonuclease]] that processes potentially harmful double-stranded RNA (dsRNA) into microRNA and small-interfering RNA (siRNA) to be used in the process of RNA interference. Dicer is commonly utilized by cells in order to prevent the assimilation of viral DNA into the cells’ genome. The viral DNA is butchered into smaller segments that are each about 21 nucleotides long; the cut take places at the 5’ phosphate and the 3’ hydroxyl, and usually includes a 2 nucleotide overhang. There is a single processing center in HS Dicer implying that there are two catalytic sites which help form products with the 2 3' overhang. These newly formed segments attach themselves to single stranded mRNA which ultimately leads to mRNA degradation by the cell and translational suppression. The dicer enzyme in humans contains three domains: the <scene name='70/706244/Rnase_iii_1/1'>RNase III 1</scene>, <scene name='70/706244/Rnase_iii_2/1'>RNase III 2</scene>, and the <scene name='70/706244/Paz_domain/1'>Paz Domain</scene>.<ref>PMID: 16410517</ref> There are three classes of RNase III proteins which are divided into categories called Escherichia coli RNase III, <scene name='70/706244/Drosha/1'>Drosha</scene>, and Dicer which are given the numbers one, two, and three respectively. The Escherichia coli RNase III class has one domain while the Drosha and dicer have two domains each. There is no evidence of the first class of enzymes in mammals. <br />
<br />
<br />
==Structure==<br />
Human Dicer (hDicer) is a <scene name='70/706244/4nh3_dimer/1'>dimer</scene>. Each chain is a large multidomain enzyme whose C-terminal half includes a PAZ domain, a pair of tandem RNase III domains, and a double-stranded RNA-binding domain.<ref>PMID: 17920623</ref> There are four <scene name='70/706244/Mg_2eb1/1'>magnesium</scene> ions that bind to the hDicer RNase IIIb homodimer. There are oxygen ligands bonded to each Magnesium, which create an <scene name='70/706244/Mg_2eb1/3'>octahedral</scene> geometry on each Magnesium. The <scene name='70/706244/Mg_2eb1/5'>amino acids</scene> amino acids present on the oxygen ligands are Glutamic Acid and Aspartic Acid.<br />
<br />
==Pathology==<br />
Mutations involving the dicer protein have been linked to the development of diseases in humans. <br />
<br />
== References ==<br />
<references/></div>Sam Hayeshttps://proteopedia.org/index.php?title=Dicer&diff=2602566Dicer2016-05-23T15:34:09Z<p>Sam Hayes: Undo revision 2602565 by Sam Hayes (Talk)</p>
<hr />
<div>==Dicer==<br />
<StructureSection load='4NH3' size='340' side='right' caption="Dicer' scene='4NH3_dimer/1'><br />
<br />
<br />
Dicer is a type of [[Ribonuclease]] that processes potentially harmful double-stranded RNA (dsRNA) into microRNA and small-interfering RNA (siRNA) to be used in the process of RNA interference. Dicer is commonly utilized by cells in order to prevent the assimilation of viral DNA into the cells’ genome. The viral DNA is butchered into smaller segments that are each about 21 nucleotides long; the cut take places at the 5’ phosphate and the 3’ hydroxyl, and usually includes a 2 nucleotide overhang. There is a single processing center in HS Dicer implying that there are two catalytic sites which help form products with the 2 3' overhang. These newly formed segments attach themselves to single stranded mRNA which ultimately leads to mRNA degradation by the cell and translational suppression. The dicer enzyme in humans contains three domains: the <scene name='70/706244/Rnase_iii_1/1'>RNase III 1</scene>, <scene name='70/706244/Rnase_iii_2/1'>RNase III 2</scene>, and the <scene name='70/706244/Paz_domain/1'>Paz Domain</scene>.<ref>PMID: 16410517</ref> There are three classes of RNase III proteins which are divided into categories called Escherichia coli RNase III, <scene name='70/706244/Drosha/1'>Drosha</scene>, and Dicer which are given the numbers one, two, and three respectively. The Escherichia coli RNase III class has one domain while the Drosha and dicer have two domains each. There is no evidence of the first class of enzymes in mammals. <br />
<br />
<br />
==Structure==<br />
Human Dicer (hDicer) is a <scene name='70/706244/4nh3_dimer/1'>dimer</scene>. Each chain is a large multidomain enzyme whose C-terminal half includes a PAZ domain, a pair of tandem RNase III domains, and a double-stranded RNA-binding domain.<ref>PMID: 17920623</ref> There are four <scene name='70/706244/Mg_2eb1/1'>magnesium</scene> ions that bind to the hDicer RNase IIIb homodimer. There are oxygen ligands bonded to each Magnesium, which create an <scene name='70/706244/Mg_2eb1/3'>octahedral</scene> geometry on each Magnesium. The <scene name='70/706244/Mg_2eb1/5'>amino acids</scene> amino acids present on the oxygen ligands are Glutamic Acid and Aspartic Acid.<br />
<br />
</StructureSection><br />
<br />
==Pathology==<br />
Mutations involving the dicer protein have been linked to the development of diseases in humans. <br />
<br />
== References ==<br />
<references/></div>Sam Hayeshttps://proteopedia.org/index.php?title=Dicer&diff=2602565Dicer2016-05-23T15:33:35Z<p>Sam Hayes: </p>
<hr />
<div>==Dicer==<br />
<br />
==Introduction==<br />
Dicer is a type of [[Ribonuclease]] that processes potentially harmful double-stranded RNA (dsRNA) into microRNA and small-interfering RNA (siRNA) to be used in the process of RNA interference. Dicer is commonly utilized by cells in order to prevent the assimilation of viral DNA into the cells’ genome. The viral DNA is butchered into smaller segments that are each about 21 nucleotides long; the cut take places at the 5’ phosphate and the 3’ hydroxyl, and usually includes a 2 nucleotide overhang. There is a single processing center in HS Dicer implying that there are two catalytic sites which help form products with the 2 3' overhang. These newly formed segments attach themselves to single stranded mRNA which ultimately leads to mRNA degradation by the cell and translational suppression. The dicer enzyme in humans contains three domains: the <scene name='70/706244/Rnase_iii_1/1'>RNase III 1</scene>, <scene name='70/706244/Rnase_iii_2/1'>RNase III 2</scene>, and the <scene name='70/706244/Paz_domain/1'>Paz Domain</scene>.<ref>PMID: 16410517</ref> There are three classes of RNase III proteins which are divided into categories called Escherichia coli RNase III, <scene name='70/706244/Drosha/1'>Drosha</scene>, and Dicer which are given the numbers one, two, and three respectively. The Escherichia coli RNase III class has one domain while the Drosha and dicer have two domains each. There is no evidence of the first class of enzymes in mammals. <br />
<br />
==Structure==<br />
Human Dicer (hDicer) is a <scene name='70/706244/4nh3_dimer/1'>dimer</scene>. Each chain is a large multidomain enzyme whose C-terminal half includes a PAZ domain, a pair of tandem RNase III domains, and a double-stranded RNA-binding domain.<ref>PMID: 17920623</ref> There are four <scene name='70/706244/Mg_2eb1/1'>magnesium</scene> ions that bind to the hDicer RNase IIIb homodimer. There are oxygen ligands bonded to each Magnesium, which create an <scene name='70/706244/Mg_2eb1/3'>octahedral</scene> geometry on each Magnesium. The <scene name='70/706244/Mg_2eb1/5'>amino acids</scene> amino acids present on the oxygen ligands are Glutamic Acid and Aspartic Acid.<br />
<br />
==Pathology==<br />
Mutations involving the dicer protein have been linked to the development of diseases in humans. <br />
<br />
== References ==<br />
<references/></div>Sam Hayeshttps://proteopedia.org/index.php?title=Dicer&diff=2602564Dicer2016-05-23T15:31:48Z<p>Sam Hayes: </p>
<hr />
<div>==Dicer==<br />
<StructureSection load='4NH3' size='340' side='right' caption="Dicer' scene='4NH3_dimer/1'><br />
<br />
<br />
Dicer is a type of [[Ribonuclease]] that processes potentially harmful double-stranded RNA (dsRNA) into microRNA and small-interfering RNA (siRNA) to be used in the process of RNA interference. Dicer is commonly utilized by cells in order to prevent the assimilation of viral DNA into the cells’ genome. The viral DNA is butchered into smaller segments that are each about 21 nucleotides long; the cut take places at the 5’ phosphate and the 3’ hydroxyl, and usually includes a 2 nucleotide overhang. There is a single processing center in HS Dicer implying that there are two catalytic sites which help form products with the 2 3' overhang. These newly formed segments attach themselves to single stranded mRNA which ultimately leads to mRNA degradation by the cell and translational suppression. The dicer enzyme in humans contains three domains: the <scene name='70/706244/Rnase_iii_1/1'>RNase III 1</scene>, <scene name='70/706244/Rnase_iii_2/1'>RNase III 2</scene>, and the <scene name='70/706244/Paz_domain/1'>Paz Domain</scene>.<ref>PMID: 16410517</ref> There are three classes of RNase III proteins which are divided into categories called Escherichia coli RNase III, <scene name='70/706244/Drosha/1'>Drosha</scene>, and Dicer which are given the numbers one, two, and three respectively. The Escherichia coli RNase III class has one domain while the Drosha and dicer have two domains each. There is no evidence of the first class of enzymes in mammals. <br />
<br />
<br />
==Structure==<br />
Human Dicer (hDicer) is a <scene name='70/706244/4nh3_dimer/1'>dimer</scene>. Each chain is a large multidomain enzyme whose C-terminal half includes a PAZ domain, a pair of tandem RNase III domains, and a double-stranded RNA-binding domain.<ref>PMID: 17920623</ref> There are four <scene name='70/706244/Mg_2eb1/1'>magnesium</scene> ions that bind to the hDicer RNase IIIb homodimer. There are oxygen ligands bonded to each Magnesium, which create an <scene name='70/706244/Mg_2eb1/3'>octahedral</scene> geometry on each Magnesium. The <scene name='70/706244/Mg_2eb1/5'>amino acids</scene> amino acids present on the oxygen ligands are Glutamic Acid and Aspartic Acid.<br />
<br />
</StructureSection><br />
<br />
==Pathology==<br />
Mutations involving the dicer protein have been linked to the development of diseases in humans. <br />
<br />
== References ==<br />
<references/></div>Sam Hayeshttps://proteopedia.org/index.php?title=Dicer&diff=2602561Dicer2016-05-23T15:19:56Z<p>Sam Hayes: </p>
<hr />
<div>==Dicer==<br />
<StructureSection load='4NH3' size='340' side='right' caption="Dicer' scene='4NH3_dimer/1'><br />
<br />
<br />
Dicer is a type of [[Ribonuclease]] that processes potentially harmful double-stranded RNA (dsRNA) into microRNA and small-interfering RNA (siRNA) to be used in the process of RNA interference. Dicer is commonly utilized by cells in order to prevent the assimilation of viral DNA into the cells’ genome. The viral DNA is butchered into smaller segments that are each about 21 nucleotides long; the cut take places at the 5’ phosphate and the 3’ hydroxyl, and usually includes a 2 nucleotide overhang. There is a single processing center in HS Dicer implying that there are two catalytic sites which help form products with the 2 3' overhang. These newly formed segments attach themselves to single stranded mRNA which ultimately leads to mRNA degradation by the cell and translational suppression. The dicer enzyme in humans contains three domains: the <scene name='70/706244/Rnase_iii_1/1'>RNase III 1</scene>, <scene name='70/706244/Rnase_iii_2/1'>RNase III 2</scene>, and the <scene name='70/706244/Paz_domain/1'>Paz Domain</scene>.<ref>PMID: 16410517</ref> There are three classes of RNase III proteins which are divided into categories called Escherichia coli RNase III, Drosha, and Dicer which are given the numbers one, two, and three respectively. The Escherichia coli RNase III class has one domain while the Drosha and dicer have two domains each. There is no evidence of the first class of enzymes in mammals. <br />
<br />
<br />
==Structure==<br />
Human Dicer (hDicer) is a <scene name='70/706244/4nh3_dimer/1'>dimer</scene>. Each chain is a large multidomain enzyme whose C-terminal half includes a PAZ domain, a pair of tandem RNase III domains, and a double-stranded RNA-binding domain.<ref>PMID: 17920623</ref> There are four <scene name='70/706244/Mg_2eb1/1'>magnesium</scene> ions that bind to the hDicer RNase IIIb homodimer. There are oxygen ligands bonded to each Magnesium, which create an <scene name='70/706244/Mg_2eb1/3'>octahedral</scene> geometry on each Magnesium. The <scene name='70/706244/Mg_2eb1/5'>amino acids</scene> amino acids present on the oxygen ligands are Glutamic Acid and Aspartic Acid.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Sam Hayeshttps://proteopedia.org/index.php?title=Dicer&diff=2602560Dicer2016-05-23T15:19:18Z<p>Sam Hayes: </p>
<hr />
<div>==Dicer==<br />
<StructureSection load='4NH3' size='340' side='right' caption="Dicer' scene='4NH3_dimer/1'><br />
<br />
<br />
Dicer is a type of [[Ribonuclease]] that processes potentially harmful double-stranded RNA (dsRNA) into microRNA and small-interfering RNA (siRNA) to be used in the process of RNA interference. Dicer is commonly utilized by cells in order to prevent the assimilation of viral DNA into the cells’ genome. The viral DNA is butchered into smaller segments that are each about 21 nucleotides long; the cut take places at the 5’ phosphate and the 3’ hydroxyl, and usually includes a 2 nucleotide overhang. There is a single processing center in HS Dicer implying that there are two catalytic sites which help form products with the 2 3' overhang. These newly formed segments attach themselves to single stranded mRNA which ultimately leads to mRNA degradation by the cell and translational suppression. The dicer enzyme in humans contains three domains: the <scene name='70/706244/Rnase_iii_1/1'>RNase III 1</scene>, <scene name='70/706244/Rnase_iii_2/1'>RNase III 2</scene>, and the <scene name='70/706244/Paz_domain/1'>Paz Domain</scene>.<ref>16410517</ref> There are three classes of RNase III proteins which are divided into categories called Escherichia coli RNase III, Drosha, and Dicer which are given the numbers one, two, and three respectively. The Escherichia coli RNase III class has one domain while the Drosha and dicer have two domains each. There is no evidence of the first class of enzymes in mammals. <br />
<br />
<br />
==Structure==<br />
Human Dicer (hDicer) is a <scene name='70/706244/4nh3_dimer/1'>dimer</scene>. Each chain is a large multidomain enzyme whose C-terminal half includes a PAZ domain, a pair of tandem RNase III domains, and a double-stranded RNA-binding domain.<ref>PMID: 17920623</ref> There are four <scene name='70/706244/Mg_2eb1/1'>magnesium</scene> ions that bind to the hDicer RNase IIIb homodimer. There are oxygen ligands bonded to each Magnesium, which create an <scene name='70/706244/Mg_2eb1/3'>octahedral</scene> geometry on each Magnesium. The <scene name='70/706244/Mg_2eb1/5'>amino acids</scene> amino acids present on the oxygen ligands are Glutamic Acid and Aspartic Acid.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Sam Hayeshttps://proteopedia.org/index.php?title=Dicer&diff=2602558Dicer2016-05-23T15:09:00Z<p>Sam Hayes: </p>
<hr />
<div>==Dicer==<br />
<StructureSection load='4NH3' size='340' side='right' caption="Dicer' scene='4NH3_dimer/1'><br />
<br />
<br />
Dicer is a type of [[Ribonuclease]] that processes potentially harmful double-stranded RNA (dsRNA) into microRNA and small-interfering RNA (siRNA) to be used in the process of RNA interference. Dicer is commonly utilized by cells in order to prevent the assimilation of viral DNA into the cells’ genome. The viral DNA is butchered into smaller segments that are each about 21 nucleotides long; the cut take places at the 5’ phosphate and the 3’ hydroxyl, and usually includes a 2 nucleotide overhang. There is a single processing center in HS Dicer implying that there are two catalytic sites which help form products with the 2 3' overhang. These newly formed segments attach themselves to single stranded mRNA which ultimately leads to mRNA degradation by the cell and translational suppression. The dicer enzyme in humans contains three domains: the <scene name='70/706244/Rnase_iii_1/1'>RNase III 1</scene>, <scene name='70/706244/Rnase_iii_2/1'>RNase III 2</scene>, and the <scene name='70/706244/Paz_domain/1'>Paz Domain</scene>. There are three classes of RNase III proteins which are divided into categories called Escherichia coli RNase III, Drosha, and Dicer which are given the numbers one, two, and three respectively. The Escherichia coli RNase III class has one domain while the Drosha and dicer have two domains each. There is no evidence of the first class of enzymes in mammals. <br />
<br />
<br />
==Structure==<br />
Human Dicer (hDicer) is a <scene name='70/706244/4nh3_dimer/1'>dimer</scene>. Each chain is a large multidomain enzyme whose C-terminal half includes a PAZ domain, a pair of tandem RNase III domains, and a double-stranded RNA-binding domain. There are four <scene name='70/706244/Mg_2eb1/1'>magnesium</scene> ions that bind to the hDicer RNase IIIb homodimer. There are oxygen ligands bonded to each Magnesium, which create an <scene name='70/706244/Mg_2eb1/3'>octahedral</scene> geometry on each Magnesium. The <scene name='70/706244/Mg_2eb1/5'>amino acids</scene> amino acids present on the oxygen ligands are Glutamic Acid and Aspartic Acid.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Sam Hayeshttps://proteopedia.org/index.php?title=Dicer&diff=2602557Dicer2016-05-23T15:08:31Z<p>Sam Hayes: </p>
<hr />
<div>==Dicer==<br />
<StructureSection load='4NH3' size='340' side='right' caption="Dicer' scene='4NH3_dimer/1'><br />
<br />
<br />
Dicer is a type of [[Ribonuclease]] that processes potentially harmful double-stranded RNA (dsRNA) into microRNA and small-interfering RNA (siRNA) to be used in the process of RNA interference. Dicer is commonly utilized by cells in order to prevent the assimilation of viral DNA into the cells’ genome. The viral DNA is butchered into smaller segments that are each about 21 nucleotides long; the cut take places at the 5’ phosphate and the 3’ hydroxyl, and usually includes a 2 nucleotide overhang. There is a single processing center in HS Dicer implying that there are two catalytic sites which help form products with the 2 3' overhang. These newly formed segments attach themselves to single stranded mRNA which ultimately leads to mRNA degradation by the cell and translational suppression. The dicer enzyme in humans contains three domains: the <scene name='70/706244/Rnase_iii_1/1'>RNase III 1</scene>, <scene name='70/706244/Rnase_iii_2/1'>RNase III 2</scene>, and the <scene name='70/706244/Paz_domain/1'>Paz Domain</scene><br />
. There are three classes of RNase III proteins which are divided into categories called Escherichia coli RNase III, Drosha, and Dicer which are given the numbers one, two, and three respectively. The Escherichia coli RNase III class has one domain while the Drosha and dicer have two domains each. There is no evidence of the first class of enzymes in mammals. <br />
<br />
<br />
==Structure==<br />
Human Dicer (hDicer) is a <scene name='70/706244/4nh3_dimer/1'>dimer</scene>. Each chain is a large multidomain enzyme whose C-terminal half includes a PAZ domain, a pair of tandem RNase III domains, and a double-stranded RNA-binding domain. There are four <scene name='70/706244/Mg_2eb1/1'>magnesium</scene> ions that bind to the hDicer RNase IIIb homodimer. There are oxygen ligands bonded to each Magnesium, which create an <scene name='70/706244/Mg_2eb1/3'>octahedral</scene> geometry on each Magnesium. The <scene name='70/706244/Mg_2eb1/5'>amino acids</scene> amino acids present on the oxygen ligands are Glutamic Acid and Aspartic Acid.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Sam Hayeshttps://proteopedia.org/index.php?title=Dicer&diff=2602550Dicer2016-05-23T14:12:51Z<p>Sam Hayes: </p>
<hr />
<div>==Dicer==<br />
<StructureSection load='' size='340' side='right' caption="Dicer' scene='4NH3_dimer/1'><br />
<br />
<br />
Dicer is a type of [[Ribonuclease]] that processes potentially harmful double-stranded RNA (dsRNA) into microRNA and small-interfering RNA (siRNA) to be used in the process of RNA interference. Dicer is commonly utilized by cells in order to prevent the assimilation of viral DNA into the cells’ genome. The viral DNA is butchered into smaller segments that are each about 21 nucleotides long; the cut take places at the 5’ phosphate and the 3’ hydroxyl, and usually includes a 2 nucleotide overhang. There is a single processing center in HS Dicer implying that there are two catalytic sites which help form products with the 2 3' overhang. These newly formed segments attach themselves to single stranded mRNA which ultimately leads to mRNA degradation by the cell and translational suppression. The dicer enzyme in humans contains two domains the RNase IIIa and the RNase IIIb. There are three classes of RNase III proteins which are divided into categories called Escherichia coli RNase III, Drosha, and Dicer which are given the numbers one, two, and three respectively. The Escherichia coli RNase III class has one domain while the Drosha and dicer have two domains each. There is no evidence of the first class of enzymes in mammals. <br />
<br />
<scene name='70/706244/Paz_domain/1'>Paz Domain</scene><br />
<scene name='70/706244/Rnase_iii_1/1'>RNase III 1</scene><br />
<scene name='70/706244/Rnase_iii_2/1'>RNase III 2</scene><br />
<br />
==Structure==<br />
Human Dicer (hDicer) is a <scene name='70/706244/4nh3_dimer/1'>dimer</scene>. Each chain is a large multidomain enzyme whose C-terminal half includes a PAZ domain, a pair of tandem RNase III domains, and a double-stranded RNA-binding domain. There are four <scene name='70/706244/Mg_2eb1/1'>magnesium</scene> ions that bind to the hDicer RNase IIIb homodimer. There are oxygen ligands bonded to each Magnesium, which create an <scene name='70/706244/Mg_2eb1/2'>octahedral</scene> geometry on each Magnesium.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Sam Hayeshttps://proteopedia.org/index.php?title=Dicer&diff=2602549Dicer2016-05-23T14:12:22Z<p>Sam Hayes: </p>
<hr />
<div>==Dicer==<br />
<StructureSection load='' size='340' side='right' caption="Dicer' scene='4NH3_dimer/1'><br />
<br />
<br />
Dicer is a type of [[Ribonuclease]] that processes potentially harmful double-stranded RNA (dsRNA) into microRNA and small-interfering RNA (siRNA) to be used in the process of RNA interference. Dicer is commonly utilized by cells in order to prevent the assimilation of viral DNA into the cells’ genome. The viral DNA is butchered into smaller segments that are each about 21 nucleotides long; the cut take places at the 5’ phosphate and the 3’ hydroxyl, and usually includes a 2 nucleotide overhang. There is a single processing center in HS Dicer implying that there are two catalytic sites which help form products with the 2 3' overhang. These newly formed segments attach themselves to single stranded mRNA which ultimately leads to mRNA degradation by the cell and translational suppression. The dicer enzyme in humans contains two domains the RNase IIIa and the RNase IIIb. There are three classes of RNase III proteins which are divided into categories called Escherichia coli RNase III, Drosha, and Dicer which are given the numbers one, two, and three respectively. The Escherichia coli RNase III class has one domain while the Drosha and dicer have two domains each. There is no evidence of the first class of enzymes in mammals. <br />
<br />
<scene name='70/706244/Paz_domain/1'>Paz Domain</scene><br />
<scene name='70/706244/Rnase_iii_1/1'>RNase III 1</scene><br />
<scene name='70/706244/Rnase_iii_2/1'>TextToBeDisplayed</scene><br />
<br />
==Structure==<br />
Human Dicer (hDicer) is a <scene name='70/706244/4nh3_dimer/1'>dimer</scene>. Each chain is a large multidomain enzyme whose C-terminal half includes a PAZ domain, a pair of tandem RNase III domains, and a double-stranded RNA-binding domain. There are four <scene name='70/706244/Mg_2eb1/1'>magnesium</scene> ions that bind to the hDicer RNase IIIb homodimer. There are oxygen ligands bonded to each Magnesium, which create an <scene name='70/706244/Mg_2eb1/2'>octahedral</scene> geometry on each Magnesium.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Sam Hayeshttps://proteopedia.org/index.php?title=Dicer&diff=2602548Dicer2016-05-23T14:07:20Z<p>Sam Hayes: </p>
<hr />
<div>==Dicer==<br />
<StructureSection load='' size='340' side='right' caption="Dicer' scene='4NH3_dimer/1'><br />
<br />
<br />
Dicer is a type of [[Ribonuclease]] that processes potentially harmful double-stranded RNA (dsRNA) into microRNA and small-interfering RNA (siRNA) to be used in the process of RNA interference. Dicer is commonly utilized by cells in order to prevent the assimilation of viral DNA into the cells’ genome. The viral DNA is butchered into smaller segments that are each about 21 nucleotides long; the cut take places at the 5’ phosphate and the 3’ hydroxyl, and usually includes a 2 nucleotide overhang. There is a single processing center in HS Dicer implying that there are two catalytic sites which help form products with the 2 3' overhang. These newly formed segments attach themselves to single stranded mRNA which ultimately leads to mRNA degradation by the cell and translational suppression. The dicer enzyme in humans contains two domains the RNase IIIa and the RNase IIIb. There are three classes of RNase III proteins which are divided into categories called Escherichia coli RNase III, Drosha, and Dicer which are given the numbers one, two, and three respectively. The Escherichia coli RNase III class has one domain while the Drosha and dicer have two domains each. There is no evidence of the first class of enzymes in mammals. <br />
<br />
<scene name='70/706244/Paz_domain/1'>Paz Domain</scene><br />
<scene name='70/706244/Rnase_iii_1/1'>RNase III 1</scene><br />
<br />
==Structure==<br />
Human Dicer (hDicer) is a <scene name='70/706244/4nh3_dimer/1'>dimer</scene>. Each chain is a large multidomain enzyme whose C-terminal half includes a PAZ domain, a pair of tandem RNase III domains, and a double-stranded RNA-binding domain. There are four <scene name='70/706244/Mg_2eb1/1'>magnesium</scene> ions that bind to the hDicer RNase IIIb homodimer. There are oxygen ligands bonded to each Magnesium, which create an <scene name='70/706244/Mg_2eb1/2'>octahedral</scene> geometry on each Magnesium.<br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Sam Hayeshttps://proteopedia.org/index.php?title=Dicer&diff=2602546Dicer2016-05-23T13:58:33Z<p>Sam Hayes: </p>
<hr />
<div>==Dicer==<br />
<StructureSection load='' size='340' side='right' caption="Dicer' scene='4NH3_dimer/1'><br />
<br />
<br />
Dicer is a type of [[Ribonuclease]] that processes potentially harmful double-stranded RNA (dsRNA) into microRNA and small-interfering RNA (siRNA) to be used in the process of RNA interference. Dicer is commonly utilized by cells in order to prevent the assimilation of viral DNA into the cells’ genome. The viral DNA is butchered into smaller segments that are each about 21 nucleotides long; the cut take places at the 5’ phosphate and the 3’ hydroxyl, and usually includes a 2 nucleotide overhang. There is a single processing center in HS Dicer implying that there are two catalytic sites which help form products with the 2 3' overhang. These newly formed segments attach themselves to single stranded mRNA which ultimately leads to mRNA degradation by the cell and translational suppression. The dicer enzyme in humans contains two domains the RNase IIIa and the RNase IIIb. There are three classes of RNase III proteins which are divided into categories called Escherichia coli RNase III, Drosha, and Dicer which are given the numbers one, two, and three respectively. The Escherichia coli RNase III class has one domain while the Drosha and dicer have two domains each. There is no evidence of the first class of enzymes in mammals. <br />
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<scene name='70/706244/Paz_domain/1'>Paz Domain</scene><br />
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==Structure==<br />
Human Dicer (hDicer) is a <scene name='70/706244/4nh3_dimer/1'>dimer</scene>. Each chain is a large multidomain enzyme whose C-terminal half includes a PAZ domain, a pair of tandem RNase III domains, and a double-stranded RNA-binding domain. There are four <scene name='70/706244/Mg_2eb1/1'>magnesium</scene> ions that bind to the Homo Sapien Dicer RNase IIIb homodimer. There are oxygen ligands bonded to each Magnesium, which create an octahedral geometry on each Magnesium.<br />
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</StructureSection><br />
== References ==<br />
<references/></div>Sam Hayeshttps://proteopedia.org/index.php?title=User:Sam_Hayes&diff=2602545User:Sam Hayes2016-05-23T13:20:06Z<p>Sam Hayes: </p>
<hr />
<div>* Full Real Name:<br />
Samuel Hayes<br />
* Position:<br />
Student<br />
* Institution (NO ABBREVIATIONS):<br />
Wabash College<br />
* City, State/Province, Country:<br />
Crawfordsville, IN, United States<br />
* Field of Expertise or Study:<br />
Biochemistry research intern</div>Sam Hayeshttps://proteopedia.org/index.php?title=Dicer&diff=2602514Dicer2016-05-18T15:46:55Z<p>Sam Hayes: </p>
<hr />
<div>==Dicer==<br />
<StructureSection load='' size='340' side='right' caption="Dicer' scene='4NH3_dimer/1'><br />
<br />
<br />
Dicer is a type of [[Ribonuclease]] that processes potentially harmful double-stranded RNA (dsRNA) into microRNA and small-interfering RNA (siRNA) to be used in the process of RNA interference. Dicer is commonly utilized by cells in order to prevent the assimilation of viral DNA into the cells’ genome. The viral DNA is butchered into smaller segments that are each about 21 nucleotides long; the cut take places at the 5’ phosphate and the 3’ hydroxyl, and usually includes a 2 nucleotide overhang. These newly formed segments attach themselves to single stranded mRNA which ultimately leads to mRNA degradation by the cell and translational suppression. Dicer is a tool used by cells as a defense mechanism. <br />
<br />
==Structure==<br />
Human Dicer (hDicer) is a <scene name='70/706244/4nh3_dimer/1'>dimer</scene>. Each chain is a large multidomain enzyme whose C-terminal half includes a PAZ domain, a pair of tandem RNase III domains, and a double-stranded RNA-binding domain. <scene name='70/706244/Mg_2eb1/1'>magnesium</scene><br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Sam Hayeshttps://proteopedia.org/index.php?title=Dicer&diff=2602513Dicer2016-05-18T15:45:10Z<p>Sam Hayes: </p>
<hr />
<div>==Dicer==<br />
<StructureSection load='' size='340' side='right' caption="Dicer' scene='4NH3_dimer/1'><br />
<br />
<br />
Dicer is a type of [[Ribonuclease]] that processes potentially harmful double-stranded RNA (dsRNA) into microRNA and small-interfering RNA (siRNA) to be used in the process of RNA interference. Dicer is commonly utilized by cells in order to prevent the assimilation of viral DNA into the cells’ genome. The viral DNA is butchered into smaller segments that are each about 21 nucleotides long; the cut take places at the 5’ phosphate and the 3’ hydroxyl, and usually includes a 2 nucleotide overhang. These newly formed segments attach themselves to single stranded mRNA which ultimately leads to mRNA degradation by the cell and translational suppression. Dicer as a tool used by cells works as a defense mechanism. <br />
<br />
==Structure==<br />
Human Dicer (hDicer) is a <scene name='70/706244/4nh3_dimer/1'>dimer</scene>. Each chain is a large multidomain enzyme whose C-terminal half includes a PAZ domain, a pair of tandem RNase III domains, and a double-stranded RNA-binding domain. <scene name='70/706244/Mg_2eb1/1'>magnesium</scene><br />
<br />
</StructureSection><br />
== References ==<br />
<references/></div>Sam Hayes