3thy - Revision history

OCA at 10:09, 1 March 2024

2024-03-01T10:09:13Z

← Older revision		Revision as of 10:09, 1 March 2024
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	<StructureSection load='3thy' size='340' side='right'caption='[[3thy]], [[Resolution\|resolution]] 2.89Å' scene=''>		<StructureSection load='3thy' size='340' side='right'caption='[[3thy]], [[Resolution\|resolution]] 2.89Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3thy]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3THY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3THY FirstGlance]. <br>		<table><tr><td colspan='2'>[[3thy]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3THY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3THY FirstGlance]. <br>
	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=ADP:ADENOSINE~~-~~5-DIPHOSPHATE'>ADP</scene>~~</td></tr>		</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.894Å</td></tr>
	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"><~~div style~~='~~overflow~~: ~~auto; max~~-~~height: 3em;~~'>~~[[3thw\|3thw]], [[3thx\|3thx]], [[3thz\|3thz]]~~</~~div></td></tr>~~		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene></td></tr>
	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b~~></td><td class="sblockDat">MSH2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), DUC1, DUG, MSH3 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3thy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3thy OCA], [https://pdbe.org/3thy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3thy RCSB], [https://www.ebi.ac.uk/pdbsum/3thy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3thy ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3thy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3thy OCA], [https://pdbe.org/3thy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3thy RCSB], [https://www.ebi.ac.uk/pdbsum/3thy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3thy ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[https://www.uniprot.org/uniprot/MSH2_HUMAN MSH2_HUMAN]] Defects in MSH2 are the cause of hereditary non-polyposis colorectal cancer type 1 (HNPCC1) [MIM:[https://omim.org/entry/120435 120435]]. Mutations in more than one gene locus can be involved alone or in combination in the production of the HNPCC phenotype (also called Lynch syndrome). Most families with clinically recognized HNPCC have mutations in either MLH1 or MSH2 genes. HNPCC is an autosomal, dominantly inherited disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early onset colorectal carcinoma (CRC) and extra-colonic cancers of the gastrointestinal, urological and female reproductive tracts. HNPCC is reported to be the most common form of inherited colorectal cancer in the Western world. Cancers in HNPCC originate within benign neoplastic polyps termed adenomas. Clinically, HNPCC is often divided into two subgroups. Type I: hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II: patients have an increased risk for cancers in certain tissues such as the uterus, ovary, breast, stomach, small intestine, skin, and larynx in addition to the colon. Diagnosis of classical HNPCC is based on the Amsterdam criteria: 3 or more relatives affected by colorectal cancer, one a first degree relative of the other two; 2 or more generation affected; 1 or more colorectal cancers presenting before 50 years of age; exclusion of hereditary polyposis syndromes. The term "suspected HNPCC" or "incomplete HNPCC" can be used to describe families who do not or only partially fulfill the Amsterdam criteria, but in whom a genetic basis for colon cancer is strongly suspected. MSH2 mutations may predispose to hematological malignancies and multiple cafe-au-lait spots.<ref>PMID:8261515</ref> <ref>PMID:9889267</ref> <ref>PMID:7874129</ref> <ref>PMID:8872463</ref> <ref>PMID:8700523</ref> <ref>PMID:9311737</ref> <ref>PMID:9240418</ref> <ref>PMID:9419403</ref> <ref>PMID:9048925</ref> <ref>PMID:9298827</ref> <ref>PMID:9718327</ref> <ref>PMID:9559627</ref> <ref>PMID:10375096</ref> <ref>PMID:10573010</ref> <ref>PMID:10386556</ref> <ref>PMID:10528862</ref> <ref>PMID:10777691</ref> <ref>PMID:10612836</ref> <ref>PMID:10829038</ref> <ref>PMID:12132870</ref> <ref>PMID:11726306</ref> <ref>PMID:12373605</ref> <ref>PMID:11920458</ref> <ref>PMID:12124176</ref> <ref>PMID:12112654</ref> <ref>PMID:12200596</ref> <ref>PMID:11870161</ref> <ref>PMID:12362047</ref> <ref>PMID:12658575</ref> <ref>PMID:12655564</ref> <ref>PMID:12655568</ref> <ref>PMID:14635101</ref> <ref>PMID:15046096</ref> <ref>PMID:15300854</ref> <ref>PMID:15365995</ref> <ref>PMID:15613555</ref> <ref>PMID:15342696</ref> <ref>PMID:15896463</ref> <ref>PMID:15996210</ref> <ref>PMID:15870828</ref> <ref>PMID:15991316</ref> <ref>PMID:16451135</ref> <ref>PMID:17101317</ref> <ref>PMID:17128465</ref> <ref>PMID:18625694</ref> <ref>PMID:18951462</ref> <ref>PMID:18561205</ref> <ref>PMID:18781619</ref> <ref>PMID:18822302</ref> <ref>PMID:22102614</ref> <ref>PMID:22371642</ref> Defects in MSH2 are a cause of Muir-Torre syndrome (MRTES) [MIM:[https://omim.org/entry/158320 158320]]. Rare autosomal dominant disorder characterized by sebaceous neoplasms and visceral malignancy.<ref>PMID:7713503</ref> Defects in MSH2 are a cause of susceptibility to endometrial cancer (ENDMC) [MIM:[https://omim.org/entry/608089 608089]].		[https://www.uniprot.org/uniprot/MSH2_HUMAN MSH2_HUMAN] Defects in MSH2 are the cause of hereditary non-polyposis colorectal cancer type 1 (HNPCC1) [MIM:[https://omim.org/entry/120435 120435]. Mutations in more than one gene locus can be involved alone or in combination in the production of the HNPCC phenotype (also called Lynch syndrome). Most families with clinically recognized HNPCC have mutations in either MLH1 or MSH2 genes. HNPCC is an autosomal, dominantly inherited disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early onset colorectal carcinoma (CRC) and extra-colonic cancers of the gastrointestinal, urological and female reproductive tracts. HNPCC is reported to be the most common form of inherited colorectal cancer in the Western world. Cancers in HNPCC originate within benign neoplastic polyps termed adenomas. Clinically, HNPCC is often divided into two subgroups. Type I: hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II: patients have an increased risk for cancers in certain tissues such as the uterus, ovary, breast, stomach, small intestine, skin, and larynx in addition to the colon. Diagnosis of classical HNPCC is based on the Amsterdam criteria: 3 or more relatives affected by colorectal cancer, one a first degree relative of the other two; 2 or more generation affected; 1 or more colorectal cancers presenting before 50 years of age; exclusion of hereditary polyposis syndromes. The term "suspected HNPCC" or "incomplete HNPCC" can be used to describe families who do not or only partially fulfill the Amsterdam criteria, but in whom a genetic basis for colon cancer is strongly suspected. MSH2 mutations may predispose to hematological malignancies and multiple cafe-au-lait spots.<ref>PMID:8261515</ref> <ref>PMID:9889267</ref> <ref>PMID:7874129</ref> <ref>PMID:8872463</ref> <ref>PMID:8700523</ref> <ref>PMID:9311737</ref> <ref>PMID:9240418</ref> <ref>PMID:9419403</ref> <ref>PMID:9048925</ref> <ref>PMID:9298827</ref> <ref>PMID:9718327</ref> <ref>PMID:9559627</ref> <ref>PMID:10375096</ref> <ref>PMID:10573010</ref> <ref>PMID:10386556</ref> <ref>PMID:10528862</ref> <ref>PMID:10777691</ref> <ref>PMID:10612836</ref> <ref>PMID:10829038</ref> <ref>PMID:12132870</ref> <ref>PMID:11726306</ref> <ref>PMID:12373605</ref> <ref>PMID:11920458</ref> <ref>PMID:12124176</ref> <ref>PMID:12112654</ref> <ref>PMID:12200596</ref> <ref>PMID:11870161</ref> <ref>PMID:12362047</ref> <ref>PMID:12658575</ref> <ref>PMID:12655564</ref> <ref>PMID:12655568</ref> <ref>PMID:14635101</ref> <ref>PMID:15046096</ref> <ref>PMID:15300854</ref> <ref>PMID:15365995</ref> <ref>PMID:15613555</ref> <ref>PMID:15342696</ref> <ref>PMID:15896463</ref> <ref>PMID:15996210</ref> <ref>PMID:15870828</ref> <ref>PMID:15991316</ref> <ref>PMID:16451135</ref> <ref>PMID:17101317</ref> <ref>PMID:17128465</ref> <ref>PMID:18625694</ref> <ref>PMID:18951462</ref> <ref>PMID:18561205</ref> <ref>PMID:18781619</ref> <ref>PMID:18822302</ref> <ref>PMID:22102614</ref> <ref>PMID:22371642</ref> Defects in MSH2 are a cause of Muir-Torre syndrome (MRTES) [MIM:[https://omim.org/entry/158320 158320]. Rare autosomal dominant disorder characterized by sebaceous neoplasms and visceral malignancy.<ref>PMID:7713503</ref> Defects in MSH2 are a cause of susceptibility to endometrial cancer (ENDMC) [MIM:[https://omim.org/entry/608089 608089].
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/MSH2_HUMAN MSH2_HUMAN]] Component of the post-replicative DNA mismatch repair system (MMR). Forms two different heterodimers: MutS alpha (MSH2-MSH6 heterodimer) and MutS beta (MSH2-MSH3 heterodimer) which binds to DNA mismatches thereby initiating DNA repair. When bound, heterodimers bend the DNA helix and shields approximately 20 base pairs. MutS alpha recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. MutS beta recognizes larger insertion-deletion loops up to 13 nucleotides long. After mismatch binding, MutS alpha or beta forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis. ATP binding and hydrolysis play a pivotal role in mismatch repair functions. The ATPase activity associated with MutS alpha regulates binding similar to a molecular switch: mismatched DNA provokes ADP-->ATP exchange, resulting in a discernible conformational transition that converts MutS alpha into a sliding clamp capable of hydrolysis-independent diffusion along the DNA backbone. This transition is crucial for mismatch repair. MutS alpha may also play a role in DNA homologous recombination repair. In melanocytes may modulate both UV-B-induced cell cycle regulation and apoptosis.<ref>PMID:9822680</ref> <ref>PMID:9822679</ref> <ref>PMID:9564049</ref> <ref>PMID:10078208</ref> <ref>PMID:10660545</ref> <ref>PMID:15064730</ref> <ref>PMID:17611581</ref>		[https://www.uniprot.org/uniprot/MSH2_HUMAN MSH2_HUMAN] Component of the post-replicative DNA mismatch repair system (MMR). Forms two different heterodimers: MutS alpha (MSH2-MSH6 heterodimer) and MutS beta (MSH2-MSH3 heterodimer) which binds to DNA mismatches thereby initiating DNA repair. When bound, heterodimers bend the DNA helix and shields approximately 20 base pairs. MutS alpha recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. MutS beta recognizes larger insertion-deletion loops up to 13 nucleotides long. After mismatch binding, MutS alpha or beta forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis. ATP binding and hydrolysis play a pivotal role in mismatch repair functions. The ATPase activity associated with MutS alpha regulates binding similar to a molecular switch: mismatched DNA provokes ADP-->ATP exchange, resulting in a discernible conformational transition that converts MutS alpha into a sliding clamp capable of hydrolysis-independent diffusion along the DNA backbone. This transition is crucial for mismatch repair. MutS alpha may also play a role in DNA homologous recombination repair. In melanocytes may modulate both UV-B-induced cell cycle regulation and apoptosis.<ref>PMID:9822680</ref> <ref>PMID:9822679</ref> <ref>PMID:9564049</ref> <ref>PMID:10078208</ref> <ref>PMID:10660545</ref> <ref>PMID:15064730</ref> <ref>PMID:17611581</ref>
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	DNA mismatch repair corrects replication errors, thus reducing mutation rates and microsatellite instability. Genetic defects in this pathway cause Lynch syndrome and various cancers in humans. Binding of a mispaired or unpaired base by bacterial MutS and eukaryotic MutSalpha is well characterized. We report here crystal structures of human MutSbeta in complex with DNA containing insertion-deletion loops (IDL) of two, three, four or six unpaired nucleotides. In contrast to eukaryotic MutSalpha and bacterial MutS, which bind the base of a mismatched nucleotide, MutSbeta binds three phosphates in an IDL. DNA is severely bent at the IDL; unpaired bases are flipped out into the major groove and partially exposed to solvent. A normal downstream base pair can become unpaired; a single unpaired base can thereby be converted to an IDL of two nucleotides and recognized by MutSbeta. The C-terminal dimerization domains form an integral part of the MutS structure and coordinate asymmetrical ATP hydrolysis by Msh2 and Msh3 with mismatch binding to signal for repair.

	Mechanism of mismatch recognition revealed by human MutSbeta bound to unpaired DNA loops.,Gupta S, Gellert M, Yang W Nat Struct Mol Biol. 2011 Dec 18;19(1):72-8. doi: 10.1038/nsmb.2175. PMID:22179786<ref>PMID:22179786</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 3thy" style="background-color:#fffaf0;"></div~~>

	==See Also==		==See Also==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Yang, W]]		[[Category: Yang W]]
	~~[[Category: Abc family atpase]]~~
	~~[[Category: Dna binding protein-dna complex]]~~
	~~[[Category: Mismatch recognition]]~~
	~~[[Category: Mismatched unpaired idl dna~~]]

OCA at 16:58, 6 July 2022

2022-07-06T16:58:48Z

← Older revision		Revision as of 16:58, 6 July 2022
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	<StructureSection load='3thy' size='340' side='right'caption='[[3thy]], [[Resolution\|resolution]] 2.89Å' scene=''>		<StructureSection load='3thy' size='340' side='right'caption='[[3thy]], [[Resolution\|resolution]] 2.89Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3thy]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3THY OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3THY FirstGlance]. <br>		<table><tr><td colspan='2'>[[3thy]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3THY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3THY FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3thw\|3thw]], [[3thx\|3thx]], [[3thz\|3thz]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3thw\|3thw]], [[3thx\|3thx]], [[3thz\|3thz]]</div></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MSH2 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), DUC1, DUG, MSH3 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MSH2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), DUC1, DUG, MSH3 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3thy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3thy OCA], [~~http~~://pdbe.org/3thy PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3thy RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3thy PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3thy ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3thy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3thy OCA], [https://pdbe.org/3thy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3thy RCSB], [https://www.ebi.ac.uk/pdbsum/3thy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3thy ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[~~http~~://www.uniprot.org/uniprot/MSH2_HUMAN MSH2_HUMAN]] Defects in MSH2 are the cause of hereditary non-polyposis colorectal cancer type 1 (HNPCC1) [MIM:[~~http~~://omim.org/entry/120435 120435]]. Mutations in more than one gene locus can be involved alone or in combination in the production of the HNPCC phenotype (also called Lynch syndrome). Most families with clinically recognized HNPCC have mutations in either MLH1 or MSH2 genes. HNPCC is an autosomal, dominantly inherited disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early onset colorectal carcinoma (CRC) and extra-colonic cancers of the gastrointestinal, urological and female reproductive tracts. HNPCC is reported to be the most common form of inherited colorectal cancer in the Western world. Cancers in HNPCC originate within benign neoplastic polyps termed adenomas. Clinically, HNPCC is often divided into two subgroups. Type I: hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II: patients have an increased risk for cancers in certain tissues such as the uterus, ovary, breast, stomach, small intestine, skin, and larynx in addition to the colon. Diagnosis of classical HNPCC is based on the Amsterdam criteria: 3 or more relatives affected by colorectal cancer, one a first degree relative of the other two; 2 or more generation affected; 1 or more colorectal cancers presenting before 50 years of age; exclusion of hereditary polyposis syndromes. The term "suspected HNPCC" or "incomplete HNPCC" can be used to describe families who do not or only partially fulfill the Amsterdam criteria, but in whom a genetic basis for colon cancer is strongly suspected. MSH2 mutations may predispose to hematological malignancies and multiple cafe-au-lait spots.<ref>PMID:8261515</ref> <ref>PMID:9889267</ref> <ref>PMID:7874129</ref> <ref>PMID:8872463</ref> <ref>PMID:8700523</ref> <ref>PMID:9311737</ref> <ref>PMID:9240418</ref> <ref>PMID:9419403</ref> <ref>PMID:9048925</ref> <ref>PMID:9298827</ref> <ref>PMID:9718327</ref> <ref>PMID:9559627</ref> <ref>PMID:10375096</ref> <ref>PMID:10573010</ref> <ref>PMID:10386556</ref> <ref>PMID:10528862</ref> <ref>PMID:10777691</ref> <ref>PMID:10612836</ref> <ref>PMID:10829038</ref> <ref>PMID:12132870</ref> <ref>PMID:11726306</ref> <ref>PMID:12373605</ref> <ref>PMID:11920458</ref> <ref>PMID:12124176</ref> <ref>PMID:12112654</ref> <ref>PMID:12200596</ref> <ref>PMID:11870161</ref> <ref>PMID:12362047</ref> <ref>PMID:12658575</ref> <ref>PMID:12655564</ref> <ref>PMID:12655568</ref> <ref>PMID:14635101</ref> <ref>PMID:15046096</ref> <ref>PMID:15300854</ref> <ref>PMID:15365995</ref> <ref>PMID:15613555</ref> <ref>PMID:15342696</ref> <ref>PMID:15896463</ref> <ref>PMID:15996210</ref> <ref>PMID:15870828</ref> <ref>PMID:15991316</ref> <ref>PMID:16451135</ref> <ref>PMID:17101317</ref> <ref>PMID:17128465</ref> <ref>PMID:18625694</ref> <ref>PMID:18951462</ref> <ref>PMID:18561205</ref> <ref>PMID:18781619</ref> <ref>PMID:18822302</ref> <ref>PMID:22102614</ref> <ref>PMID:22371642</ref> Defects in MSH2 are a cause of Muir-Torre syndrome (MRTES) [MIM:[~~http~~://omim.org/entry/158320 158320]]. Rare autosomal dominant disorder characterized by sebaceous neoplasms and visceral malignancy.<ref>PMID:7713503</ref> Defects in MSH2 are a cause of susceptibility to endometrial cancer (ENDMC) [MIM:[~~http~~://omim.org/entry/608089 608089]].		[[https://www.uniprot.org/uniprot/MSH2_HUMAN MSH2_HUMAN]] Defects in MSH2 are the cause of hereditary non-polyposis colorectal cancer type 1 (HNPCC1) [MIM:[https://omim.org/entry/120435 120435]]. Mutations in more than one gene locus can be involved alone or in combination in the production of the HNPCC phenotype (also called Lynch syndrome). Most families with clinically recognized HNPCC have mutations in either MLH1 or MSH2 genes. HNPCC is an autosomal, dominantly inherited disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early onset colorectal carcinoma (CRC) and extra-colonic cancers of the gastrointestinal, urological and female reproductive tracts. HNPCC is reported to be the most common form of inherited colorectal cancer in the Western world. Cancers in HNPCC originate within benign neoplastic polyps termed adenomas. Clinically, HNPCC is often divided into two subgroups. Type I: hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II: patients have an increased risk for cancers in certain tissues such as the uterus, ovary, breast, stomach, small intestine, skin, and larynx in addition to the colon. Diagnosis of classical HNPCC is based on the Amsterdam criteria: 3 or more relatives affected by colorectal cancer, one a first degree relative of the other two; 2 or more generation affected; 1 or more colorectal cancers presenting before 50 years of age; exclusion of hereditary polyposis syndromes. The term "suspected HNPCC" or "incomplete HNPCC" can be used to describe families who do not or only partially fulfill the Amsterdam criteria, but in whom a genetic basis for colon cancer is strongly suspected. MSH2 mutations may predispose to hematological malignancies and multiple cafe-au-lait spots.<ref>PMID:8261515</ref> <ref>PMID:9889267</ref> <ref>PMID:7874129</ref> <ref>PMID:8872463</ref> <ref>PMID:8700523</ref> <ref>PMID:9311737</ref> <ref>PMID:9240418</ref> <ref>PMID:9419403</ref> <ref>PMID:9048925</ref> <ref>PMID:9298827</ref> <ref>PMID:9718327</ref> <ref>PMID:9559627</ref> <ref>PMID:10375096</ref> <ref>PMID:10573010</ref> <ref>PMID:10386556</ref> <ref>PMID:10528862</ref> <ref>PMID:10777691</ref> <ref>PMID:10612836</ref> <ref>PMID:10829038</ref> <ref>PMID:12132870</ref> <ref>PMID:11726306</ref> <ref>PMID:12373605</ref> <ref>PMID:11920458</ref> <ref>PMID:12124176</ref> <ref>PMID:12112654</ref> <ref>PMID:12200596</ref> <ref>PMID:11870161</ref> <ref>PMID:12362047</ref> <ref>PMID:12658575</ref> <ref>PMID:12655564</ref> <ref>PMID:12655568</ref> <ref>PMID:14635101</ref> <ref>PMID:15046096</ref> <ref>PMID:15300854</ref> <ref>PMID:15365995</ref> <ref>PMID:15613555</ref> <ref>PMID:15342696</ref> <ref>PMID:15896463</ref> <ref>PMID:15996210</ref> <ref>PMID:15870828</ref> <ref>PMID:15991316</ref> <ref>PMID:16451135</ref> <ref>PMID:17101317</ref> <ref>PMID:17128465</ref> <ref>PMID:18625694</ref> <ref>PMID:18951462</ref> <ref>PMID:18561205</ref> <ref>PMID:18781619</ref> <ref>PMID:18822302</ref> <ref>PMID:22102614</ref> <ref>PMID:22371642</ref> Defects in MSH2 are a cause of Muir-Torre syndrome (MRTES) [MIM:[https://omim.org/entry/158320 158320]]. Rare autosomal dominant disorder characterized by sebaceous neoplasms and visceral malignancy.<ref>PMID:7713503</ref> Defects in MSH2 are a cause of susceptibility to endometrial cancer (ENDMC) [MIM:[https://omim.org/entry/608089 608089]].
	== Function ==		== Function ==
	[[~~http~~://www.uniprot.org/uniprot/MSH2_HUMAN MSH2_HUMAN]] Component of the post-replicative DNA mismatch repair system (MMR). Forms two different heterodimers: MutS alpha (MSH2-MSH6 heterodimer) and MutS beta (MSH2-MSH3 heterodimer) which binds to DNA mismatches thereby initiating DNA repair. When bound, heterodimers bend the DNA helix and shields approximately 20 base pairs. MutS alpha recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. MutS beta recognizes larger insertion-deletion loops up to 13 nucleotides long. After mismatch binding, MutS alpha or beta forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis. ATP binding and hydrolysis play a pivotal role in mismatch repair functions. The ATPase activity associated with MutS alpha regulates binding similar to a molecular switch: mismatched DNA provokes ADP-->ATP exchange, resulting in a discernible conformational transition that converts MutS alpha into a sliding clamp capable of hydrolysis-independent diffusion along the DNA backbone. This transition is crucial for mismatch repair. MutS alpha may also play a role in DNA homologous recombination repair. In melanocytes may modulate both UV-B-induced cell cycle regulation and apoptosis.<ref>PMID:9822680</ref> <ref>PMID:9822679</ref> <ref>PMID:9564049</ref> <ref>PMID:10078208</ref> <ref>PMID:10660545</ref> <ref>PMID:15064730</ref> <ref>PMID:17611581</ref>		[[https://www.uniprot.org/uniprot/MSH2_HUMAN MSH2_HUMAN]] Component of the post-replicative DNA mismatch repair system (MMR). Forms two different heterodimers: MutS alpha (MSH2-MSH6 heterodimer) and MutS beta (MSH2-MSH3 heterodimer) which binds to DNA mismatches thereby initiating DNA repair. When bound, heterodimers bend the DNA helix and shields approximately 20 base pairs. MutS alpha recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. MutS beta recognizes larger insertion-deletion loops up to 13 nucleotides long. After mismatch binding, MutS alpha or beta forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis. ATP binding and hydrolysis play a pivotal role in mismatch repair functions. The ATPase activity associated with MutS alpha regulates binding similar to a molecular switch: mismatched DNA provokes ADP-->ATP exchange, resulting in a discernible conformational transition that converts MutS alpha into a sliding clamp capable of hydrolysis-independent diffusion along the DNA backbone. This transition is crucial for mismatch repair. MutS alpha may also play a role in DNA homologous recombination repair. In melanocytes may modulate both UV-B-induced cell cycle regulation and apoptosis.<ref>PMID:9822680</ref> <ref>PMID:9822679</ref> <ref>PMID:9564049</ref> <ref>PMID:10078208</ref> <ref>PMID:10660545</ref> <ref>PMID:15064730</ref> <ref>PMID:17611581</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 22:		Line 22:
	</div>		</div>
	<div class="pdbe-citations 3thy" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3thy" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[DNA mismatch repair protein 3D structures\|DNA mismatch repair protein 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 11:40, 17 July 2019

2019-07-17T11:40:57Z

← Older revision		Revision as of 11:40, 17 July 2019
Line 1:		Line 1:

	==Human MutSbeta complexed with an IDL of 2 bases (Loop2) and ADP==		==Human MutSbeta complexed with an IDL of 2 bases (Loop2) and ADP==
	<StructureSection load='3thy' size='340' side='right' caption='[[3thy]], [[Resolution\|resolution]] 2.89Å' scene=''>		<StructureSection load='3thy' size='340' side='right'caption='[[3thy]], [[Resolution\|resolution]] 2.89Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3thy]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3THY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3THY FirstGlance]. <br>		<table><tr><td colspan='2'>[[3thy]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3THY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3THY FirstGlance]. <br>
Line 27:		Line 27:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
			[[Category: Large Structures]]
	[[Category: Yang, W]]		[[Category: Yang, W]]
	[[Category: Abc family atpase]]		[[Category: Abc family atpase]]

OCA at 08:01, 4 August 2016

2016-08-04T08:01:19Z

← Older revision		Revision as of 08:01, 4 August 2016
Line 1:		Line 1:

	==Human MutSbeta complexed with an IDL of 2 bases (Loop2) and ADP==		==Human MutSbeta complexed with an IDL of 2 bases (Loop2) and ADP==
	<StructureSection load='3thy' size='340' side='right' caption='[[3thy]], [[Resolution\|resolution]] 2.89Å' scene=''>		<StructureSection load='3thy' size='340' side='right' caption='[[3thy]], [[Resolution\|resolution]] 2.89Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3thy]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3THY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3THY FirstGlance]. <br>		<table><tr><td colspan='2'>[[3thy]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3THY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3THY FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3thw\|3thw]], [[3thx\|3thx]], [[3thz\|3thz]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3thw\|3thw]], [[3thx\|3thx]], [[3thz\|3thz]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MSH2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~]), DUC1, DUG, MSH3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MSH2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), DUC1, DUG, MSH3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3thy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3thy OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3thy RCSB], [http://www.ebi.ac.uk/pdbsum/3thy PDBsum]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3thy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3thy OCA], [http://pdbe.org/3thy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3thy RCSB], [http://www.ebi.ac.uk/pdbsum/3thy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3thy ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 20:		Line 21:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
			<div class="pdbe-citations 3thy" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Homo sapiens~~]]		[[Category: Human]]
	[[Category: Yang, W]]		[[Category: Yang, W]]
	[[Category: Abc family atpase]]		[[Category: Abc family atpase]]

OCA at 07:15, 21 December 2014

2014-12-21T07:15:27Z

← Older revision		Revision as of 07:15, 21 December 2014
Line 1:		Line 1:
	~~{{STRUCTURE_3thy\| PDB=3thy \| SCENE= }}~~		==Human MutSbeta complexed with an IDL of 2 bases (Loop2) and ADP==
	===Human MutSbeta complexed with an IDL of 2 bases (Loop2) and ADP===		<StructureSection load='3thy' size='340' side='right' caption='[[3thy]], [[Resolution\|resolution]] 2.89Å' scene=''>
	~~{{ABSTRACT_PUBMED_22179786}}~~		== Structural highlights ==
			<table><tr><td colspan='2'>[[3thy]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3THY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3THY FirstGlance]. <br>
	==Disease==		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene></td></tr>
			<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3thw\|3thw]], [[3thx\|3thx]], [[3thz\|3thz]]</td></tr>
			<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MSH2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), DUC1, DUG, MSH3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
			<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3thy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3thy OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3thy RCSB], [http://www.ebi.ac.uk/pdbsum/3thy PDBsum]</span></td></tr>
			</table>
			== Disease ==
	[[http://www.uniprot.org/uniprot/MSH2_HUMAN MSH2_HUMAN]] Defects in MSH2 are the cause of hereditary non-polyposis colorectal cancer type 1 (HNPCC1) [MIM:[http://omim.org/entry/120435 120435]]. Mutations in more than one gene locus can be involved alone or in combination in the production of the HNPCC phenotype (also called Lynch syndrome). Most families with clinically recognized HNPCC have mutations in either MLH1 or MSH2 genes. HNPCC is an autosomal, dominantly inherited disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early onset colorectal carcinoma (CRC) and extra-colonic cancers of the gastrointestinal, urological and female reproductive tracts. HNPCC is reported to be the most common form of inherited colorectal cancer in the Western world. Cancers in HNPCC originate within benign neoplastic polyps termed adenomas. Clinically, HNPCC is often divided into two subgroups. Type I: hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II: patients have an increased risk for cancers in certain tissues such as the uterus, ovary, breast, stomach, small intestine, skin, and larynx in addition to the colon. Diagnosis of classical HNPCC is based on the Amsterdam criteria: 3 or more relatives affected by colorectal cancer, one a first degree relative of the other two; 2 or more generation affected; 1 or more colorectal cancers presenting before 50 years of age; exclusion of hereditary polyposis syndromes. The term "suspected HNPCC" or "incomplete HNPCC" can be used to describe families who do not or only partially fulfill the Amsterdam criteria, but in whom a genetic basis for colon cancer is strongly suspected. MSH2 mutations may predispose to hematological malignancies and multiple cafe-au-lait spots.<ref>PMID:8261515</ref> <ref>PMID:9889267</ref> <ref>PMID:7874129</ref> <ref>PMID:8872463</ref> <ref>PMID:8700523</ref> <ref>PMID:9311737</ref> <ref>PMID:9240418</ref> <ref>PMID:9419403</ref> <ref>PMID:9048925</ref> <ref>PMID:9298827</ref> <ref>PMID:9718327</ref> <ref>PMID:9559627</ref> <ref>PMID:10375096</ref> <ref>PMID:10573010</ref> <ref>PMID:10386556</ref> <ref>PMID:10528862</ref> <ref>PMID:10777691</ref> <ref>PMID:10612836</ref> <ref>PMID:10829038</ref> <ref>PMID:12132870</ref> <ref>PMID:11726306</ref> <ref>PMID:12373605</ref> <ref>PMID:11920458</ref> <ref>PMID:12124176</ref> <ref>PMID:12112654</ref> <ref>PMID:12200596</ref> <ref>PMID:11870161</ref> <ref>PMID:12362047</ref> <ref>PMID:12658575</ref> <ref>PMID:12655564</ref> <ref>PMID:12655568</ref> <ref>PMID:14635101</ref> <ref>PMID:15046096</ref> <ref>PMID:15300854</ref> <ref>PMID:15365995</ref> <ref>PMID:15613555</ref> <ref>PMID:15342696</ref> <ref>PMID:15896463</ref> <ref>PMID:15996210</ref> <ref>PMID:15870828</ref> <ref>PMID:15991316</ref> <ref>PMID:16451135</ref> <ref>PMID:17101317</ref> <ref>PMID:17128465</ref> <ref>PMID:18625694</ref> <ref>PMID:18951462</ref> <ref>PMID:18561205</ref> <ref>PMID:18781619</ref> <ref>PMID:18822302</ref> <ref>PMID:22102614</ref> <ref>PMID:22371642</ref> Defects in MSH2 are a cause of Muir-Torre syndrome (MRTES) [MIM:[http://omim.org/entry/158320 158320]]. Rare autosomal dominant disorder characterized by sebaceous neoplasms and visceral malignancy.<ref>PMID:7713503</ref> Defects in MSH2 are a cause of susceptibility to endometrial cancer (ENDMC) [MIM:[http://omim.org/entry/608089 608089]].		[[http://www.uniprot.org/uniprot/MSH2_HUMAN MSH2_HUMAN]] Defects in MSH2 are the cause of hereditary non-polyposis colorectal cancer type 1 (HNPCC1) [MIM:[http://omim.org/entry/120435 120435]]. Mutations in more than one gene locus can be involved alone or in combination in the production of the HNPCC phenotype (also called Lynch syndrome). Most families with clinically recognized HNPCC have mutations in either MLH1 or MSH2 genes. HNPCC is an autosomal, dominantly inherited disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early onset colorectal carcinoma (CRC) and extra-colonic cancers of the gastrointestinal, urological and female reproductive tracts. HNPCC is reported to be the most common form of inherited colorectal cancer in the Western world. Cancers in HNPCC originate within benign neoplastic polyps termed adenomas. Clinically, HNPCC is often divided into two subgroups. Type I: hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II: patients have an increased risk for cancers in certain tissues such as the uterus, ovary, breast, stomach, small intestine, skin, and larynx in addition to the colon. Diagnosis of classical HNPCC is based on the Amsterdam criteria: 3 or more relatives affected by colorectal cancer, one a first degree relative of the other two; 2 or more generation affected; 1 or more colorectal cancers presenting before 50 years of age; exclusion of hereditary polyposis syndromes. The term "suspected HNPCC" or "incomplete HNPCC" can be used to describe families who do not or only partially fulfill the Amsterdam criteria, but in whom a genetic basis for colon cancer is strongly suspected. MSH2 mutations may predispose to hematological malignancies and multiple cafe-au-lait spots.<ref>PMID:8261515</ref> <ref>PMID:9889267</ref> <ref>PMID:7874129</ref> <ref>PMID:8872463</ref> <ref>PMID:8700523</ref> <ref>PMID:9311737</ref> <ref>PMID:9240418</ref> <ref>PMID:9419403</ref> <ref>PMID:9048925</ref> <ref>PMID:9298827</ref> <ref>PMID:9718327</ref> <ref>PMID:9559627</ref> <ref>PMID:10375096</ref> <ref>PMID:10573010</ref> <ref>PMID:10386556</ref> <ref>PMID:10528862</ref> <ref>PMID:10777691</ref> <ref>PMID:10612836</ref> <ref>PMID:10829038</ref> <ref>PMID:12132870</ref> <ref>PMID:11726306</ref> <ref>PMID:12373605</ref> <ref>PMID:11920458</ref> <ref>PMID:12124176</ref> <ref>PMID:12112654</ref> <ref>PMID:12200596</ref> <ref>PMID:11870161</ref> <ref>PMID:12362047</ref> <ref>PMID:12658575</ref> <ref>PMID:12655564</ref> <ref>PMID:12655568</ref> <ref>PMID:14635101</ref> <ref>PMID:15046096</ref> <ref>PMID:15300854</ref> <ref>PMID:15365995</ref> <ref>PMID:15613555</ref> <ref>PMID:15342696</ref> <ref>PMID:15896463</ref> <ref>PMID:15996210</ref> <ref>PMID:15870828</ref> <ref>PMID:15991316</ref> <ref>PMID:16451135</ref> <ref>PMID:17101317</ref> <ref>PMID:17128465</ref> <ref>PMID:18625694</ref> <ref>PMID:18951462</ref> <ref>PMID:18561205</ref> <ref>PMID:18781619</ref> <ref>PMID:18822302</ref> <ref>PMID:22102614</ref> <ref>PMID:22371642</ref> Defects in MSH2 are a cause of Muir-Torre syndrome (MRTES) [MIM:[http://omim.org/entry/158320 158320]]. Rare autosomal dominant disorder characterized by sebaceous neoplasms and visceral malignancy.<ref>PMID:7713503</ref> Defects in MSH2 are a cause of susceptibility to endometrial cancer (ENDMC) [MIM:[http://omim.org/entry/608089 608089]].
			== Function ==
	==Function==
	[[http://www.uniprot.org/uniprot/MSH2_HUMAN MSH2_HUMAN]] Component of the post-replicative DNA mismatch repair system (MMR). Forms two different heterodimers: MutS alpha (MSH2-MSH6 heterodimer) and MutS beta (MSH2-MSH3 heterodimer) which binds to DNA mismatches thereby initiating DNA repair. When bound, heterodimers bend the DNA helix and shields approximately 20 base pairs. MutS alpha recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. MutS beta recognizes larger insertion-deletion loops up to 13 nucleotides long. After mismatch binding, MutS alpha or beta forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis. ATP binding and hydrolysis play a pivotal role in mismatch repair functions. The ATPase activity associated with MutS alpha regulates binding similar to a molecular switch: mismatched DNA provokes ADP-->ATP exchange, resulting in a discernible conformational transition that converts MutS alpha into a sliding clamp capable of hydrolysis-independent diffusion along the DNA backbone. This transition is crucial for mismatch repair. MutS alpha may also play a role in DNA homologous recombination repair. In melanocytes may modulate both UV-B-induced cell cycle regulation and apoptosis.<ref>PMID:9822680</ref> <ref>PMID:9822679</ref> <ref>PMID:9564049</ref> <ref>PMID:10078208</ref> <ref>PMID:10660545</ref> <ref>PMID:15064730</ref> <ref>PMID:17611581</ref>		[[http://www.uniprot.org/uniprot/MSH2_HUMAN MSH2_HUMAN]] Component of the post-replicative DNA mismatch repair system (MMR). Forms two different heterodimers: MutS alpha (MSH2-MSH6 heterodimer) and MutS beta (MSH2-MSH3 heterodimer) which binds to DNA mismatches thereby initiating DNA repair. When bound, heterodimers bend the DNA helix and shields approximately 20 base pairs. MutS alpha recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. MutS beta recognizes larger insertion-deletion loops up to 13 nucleotides long. After mismatch binding, MutS alpha or beta forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis. ATP binding and hydrolysis play a pivotal role in mismatch repair functions. The ATPase activity associated with MutS alpha regulates binding similar to a molecular switch: mismatched DNA provokes ADP-->ATP exchange, resulting in a discernible conformational transition that converts MutS alpha into a sliding clamp capable of hydrolysis-independent diffusion along the DNA backbone. This transition is crucial for mismatch repair. MutS alpha may also play a role in DNA homologous recombination repair. In melanocytes may modulate both UV-B-induced cell cycle regulation and apoptosis.<ref>PMID:9822680</ref> <ref>PMID:9822679</ref> <ref>PMID:9564049</ref> <ref>PMID:10078208</ref> <ref>PMID:10660545</ref> <ref>PMID:15064730</ref> <ref>PMID:17611581</ref>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			DNA mismatch repair corrects replication errors, thus reducing mutation rates and microsatellite instability. Genetic defects in this pathway cause Lynch syndrome and various cancers in humans. Binding of a mispaired or unpaired base by bacterial MutS and eukaryotic MutSalpha is well characterized. We report here crystal structures of human MutSbeta in complex with DNA containing insertion-deletion loops (IDL) of two, three, four or six unpaired nucleotides. In contrast to eukaryotic MutSalpha and bacterial MutS, which bind the base of a mismatched nucleotide, MutSbeta binds three phosphates in an IDL. DNA is severely bent at the IDL; unpaired bases are flipped out into the major groove and partially exposed to solvent. A normal downstream base pair can become unpaired; a single unpaired base can thereby be converted to an IDL of two nucleotides and recognized by MutSbeta. The C-terminal dimerization domains form an integral part of the MutS structure and coordinate asymmetrical ATP hydrolysis by Msh2 and Msh3 with mismatch binding to signal for repair.

	~~==About this Structure==~~		Mechanism of mismatch recognition revealed by human MutSbeta bound to unpaired DNA loops.,Gupta S, Gellert M, Yang W Nat Struct Mol Biol. 2011 Dec 18;19(1):72-8. doi: 10.1038/nsmb.2175. PMID:22179786<ref>PMID:22179786</ref>
	~~[[3thy]] is a 4 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Homo_sapiens Homo sapiens]~~. ~~Full crystallographic information is available from [http~~:/~~/oca~~.~~weizmann~~.~~ac.il~~/~~oca-bin/ocashort?id=3THY OCA].~~

	==~~Reference~~==		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	~~<ref group="xtra">PMID:022179786</ref>~~<references ~~group="xtra"~~/><~~references~~/>		</div>
			== References ==
			<references/>
			__TOC__
			</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Yang, W.]]		[[Category: Yang, W]]
	[[Category: Abc family atpase]]		[[Category: Abc family atpase]]
	[[Category: Dna binding protein-dna complex]]		[[Category: Dna binding protein-dna complex]]
	[[Category: Mismatch recognition]]		[[Category: Mismatch recognition]]
	[[Category: Mismatched unpaired idl dna]]		[[Category: Mismatched unpaired idl dna]]

OCA at 07:20, 30 June 2013

2013-06-30T07:20:52Z

← Older revision		Revision as of 07:20, 30 June 2013
Line 1:		Line 1:
	{{STRUCTURE_3thy\| PDB=3thy \| SCENE= }}		{{STRUCTURE_3thy\| PDB=3thy \| SCENE= }}
	===Human MutSbeta complexed with an IDL of 2 bases (Loop2) and ADP===		===Human MutSbeta complexed with an IDL of 2 bases (Loop2) and ADP===
	{{~~ABSTRACT_PUBMED_022179786~~}}		{{ABSTRACT_PUBMED_22179786}}

	==Disease==		==Disease==
	[[http://www.uniprot.org/uniprot/MSH2_HUMAN MSH2_HUMAN]] Defects in MSH2 are the cause of hereditary non-polyposis colorectal cancer type 1 (HNPCC1) [MIM:[http://omim.org/entry/120435 120435]]. Mutations in more than one gene locus can be involved alone or in combination in the production of the HNPCC phenotype (also called Lynch syndrome). Most families with clinically recognized HNPCC have mutations in either MLH1 or MSH2 genes. HNPCC is an autosomal, dominantly inherited disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early onset colorectal carcinoma (CRC) and extra-colonic cancers of the gastrointestinal, urological and female reproductive tracts. HNPCC is reported to be the most common form of inherited colorectal cancer in the Western world. Cancers in HNPCC originate within benign neoplastic polyps termed adenomas. Clinically, HNPCC is often divided into two subgroups. Type I: hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II: patients have an increased risk for cancers in certain tissues such as the uterus, ovary, breast, stomach, small intestine, skin, and larynx in addition to the colon. Diagnosis of classical HNPCC is based on the Amsterdam criteria: 3 or more relatives affected by colorectal cancer, one a first degree relative of the other two; 2 or more generation affected; 1 or more colorectal cancers presenting before 50 years of age; exclusion of hereditary polyposis syndromes. The term "suspected HNPCC" or "incomplete HNPCC" can be used to describe families who do not or only partially fulfill the Amsterdam criteria, but in whom a genetic basis for colon cancer is strongly suspected. MSH2 mutations may predispose to hematological malignancies and multiple cafe-au-lait spots.<ref>PMID:8261515</ref><ref>PMID:9889267</ref><ref>PMID:7874129</ref><ref>PMID:8872463</ref><ref>PMID:8700523</ref><ref>PMID:9311737</ref><ref>PMID:9240418</ref><ref>PMID:9419403</ref><ref>PMID:9048925</ref><ref>PMID:9298827</ref><ref>PMID:9718327</ref><ref>PMID:9559627</ref><ref>PMID:10375096</ref><ref>PMID:10573010</ref><ref>PMID:10386556</ref><ref>PMID:10528862</ref><ref>PMID:10777691</ref><ref>PMID:10612836</ref><ref>PMID:10829038</ref><ref>PMID:12132870</ref><ref>PMID:11726306</ref><ref>PMID:12373605</ref><ref>PMID:11920458</ref><ref>PMID:12124176</ref><ref>PMID:12112654</ref><ref>PMID:12200596</ref><ref>PMID:11870161</ref><ref>PMID:12362047</ref><ref>PMID:12658575</ref><ref>PMID:12655564</ref><ref>PMID:12655568</ref><ref>PMID:14635101</ref><ref>PMID:15046096</ref><ref>PMID:15300854</ref><ref>PMID:15365995</ref><ref>PMID:15613555</ref><ref>PMID:15342696</ref><ref>PMID:15896463</ref><ref>PMID:15996210</ref><ref>PMID:15870828</ref><ref>PMID:15991316</ref><ref>PMID:16451135</ref><ref>PMID:17101317</ref><ref>PMID:17128465</ref><ref>PMID:18625694</ref><ref>PMID:18951462</ref><ref>PMID:18561205</ref><ref>PMID:18781619</ref><ref>PMID:18822302</ref><ref>PMID:22102614</ref><ref>PMID:22371642</ref> Defects in MSH2 are a cause of Muir-Torre syndrome (MRTES) [MIM:[http://omim.org/entry/158320 158320]]. Rare autosomal dominant disorder characterized by sebaceous neoplasms and visceral malignancy.<ref>PMID:7713503</ref> Defects in MSH2 are a cause of susceptibility to endometrial cancer (ENDMC) [MIM:[http://omim.org/entry/608089 608089]].		[[http://www.uniprot.org/uniprot/MSH2_HUMAN MSH2_HUMAN]] Defects in MSH2 are the cause of hereditary non-polyposis colorectal cancer type 1 (HNPCC1) [MIM:[http://omim.org/entry/120435 120435]]. Mutations in more than one gene locus can be involved alone or in combination in the production of the HNPCC phenotype (also called Lynch syndrome). Most families with clinically recognized HNPCC have mutations in either MLH1 or MSH2 genes. HNPCC is an autosomal, dominantly inherited disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early onset colorectal carcinoma (CRC) and extra-colonic cancers of the gastrointestinal, urological and female reproductive tracts. HNPCC is reported to be the most common form of inherited colorectal cancer in the Western world. Cancers in HNPCC originate within benign neoplastic polyps termed adenomas. Clinically, HNPCC is often divided into two subgroups. Type I: hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II: patients have an increased risk for cancers in certain tissues such as the uterus, ovary, breast, stomach, small intestine, skin, and larynx in addition to the colon. Diagnosis of classical HNPCC is based on the Amsterdam criteria: 3 or more relatives affected by colorectal cancer, one a first degree relative of the other two; 2 or more generation affected; 1 or more colorectal cancers presenting before 50 years of age; exclusion of hereditary polyposis syndromes. The term "suspected HNPCC" or "incomplete HNPCC" can be used to describe families who do not or only partially fulfill the Amsterdam criteria, but in whom a genetic basis for colon cancer is strongly suspected. MSH2 mutations may predispose to hematological malignancies and multiple cafe-au-lait spots.<ref>PMID:8261515</ref> <ref>PMID:9889267</ref> <ref>PMID:7874129</ref> <ref>PMID:8872463</ref> <ref>PMID:8700523</ref> <ref>PMID:9311737</ref> <ref>PMID:9240418</ref> <ref>PMID:9419403</ref> <ref>PMID:9048925</ref> <ref>PMID:9298827</ref> <ref>PMID:9718327</ref> <ref>PMID:9559627</ref> <ref>PMID:10375096</ref> <ref>PMID:10573010</ref> <ref>PMID:10386556</ref> <ref>PMID:10528862</ref> <ref>PMID:10777691</ref> <ref>PMID:10612836</ref> <ref>PMID:10829038</ref> <ref>PMID:12132870</ref> <ref>PMID:11726306</ref> <ref>PMID:12373605</ref> <ref>PMID:11920458</ref> <ref>PMID:12124176</ref> <ref>PMID:12112654</ref> <ref>PMID:12200596</ref> <ref>PMID:11870161</ref> <ref>PMID:12362047</ref> <ref>PMID:12658575</ref> <ref>PMID:12655564</ref> <ref>PMID:12655568</ref> <ref>PMID:14635101</ref> <ref>PMID:15046096</ref> <ref>PMID:15300854</ref> <ref>PMID:15365995</ref> <ref>PMID:15613555</ref> <ref>PMID:15342696</ref> <ref>PMID:15896463</ref> <ref>PMID:15996210</ref> <ref>PMID:15870828</ref> <ref>PMID:15991316</ref> <ref>PMID:16451135</ref> <ref>PMID:17101317</ref> <ref>PMID:17128465</ref> <ref>PMID:18625694</ref> <ref>PMID:18951462</ref> <ref>PMID:18561205</ref> <ref>PMID:18781619</ref> <ref>PMID:18822302</ref> <ref>PMID:22102614</ref> <ref>PMID:22371642</ref> Defects in MSH2 are a cause of Muir-Torre syndrome (MRTES) [MIM:[http://omim.org/entry/158320 158320]]. Rare autosomal dominant disorder characterized by sebaceous neoplasms and visceral malignancy.<ref>PMID:7713503</ref> Defects in MSH2 are a cause of susceptibility to endometrial cancer (ENDMC) [MIM:[http://omim.org/entry/608089 608089]].

	==Function==		==Function==
	[[http://www.uniprot.org/uniprot/MSH2_HUMAN MSH2_HUMAN]] Component of the post-replicative DNA mismatch repair system (MMR). Forms two different heterodimers: MutS alpha (MSH2-MSH6 heterodimer) and MutS beta (MSH2-MSH3 heterodimer) which binds to DNA mismatches thereby initiating DNA repair. When bound, heterodimers bend the DNA helix and shields approximately 20 base pairs. MutS alpha recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. MutS beta recognizes larger insertion-deletion loops up to 13 nucleotides long. After mismatch binding, MutS alpha or beta forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis. ATP binding and hydrolysis play a pivotal role in mismatch repair functions. The ATPase activity associated with MutS alpha regulates binding similar to a molecular switch: mismatched DNA provokes ADP-->ATP exchange, resulting in a discernible conformational transition that converts MutS alpha into a sliding clamp capable of hydrolysis-independent diffusion along the DNA backbone. This transition is crucial for mismatch repair. MutS alpha may also play a role in DNA homologous recombination repair. In melanocytes may modulate both UV-B-induced cell cycle regulation and apoptosis.<ref>PMID:9822680</ref><ref>PMID:9822679</ref><ref>PMID:9564049</ref><ref>PMID:10078208</ref><ref>PMID:10660545</ref><ref>PMID:15064730</ref><ref>PMID:17611581</ref>		[[http://www.uniprot.org/uniprot/MSH2_HUMAN MSH2_HUMAN]] Component of the post-replicative DNA mismatch repair system (MMR). Forms two different heterodimers: MutS alpha (MSH2-MSH6 heterodimer) and MutS beta (MSH2-MSH3 heterodimer) which binds to DNA mismatches thereby initiating DNA repair. When bound, heterodimers bend the DNA helix and shields approximately 20 base pairs. MutS alpha recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. MutS beta recognizes larger insertion-deletion loops up to 13 nucleotides long. After mismatch binding, MutS alpha or beta forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis. ATP binding and hydrolysis play a pivotal role in mismatch repair functions. The ATPase activity associated with MutS alpha regulates binding similar to a molecular switch: mismatched DNA provokes ADP-->ATP exchange, resulting in a discernible conformational transition that converts MutS alpha into a sliding clamp capable of hydrolysis-independent diffusion along the DNA backbone. This transition is crucial for mismatch repair. MutS alpha may also play a role in DNA homologous recombination repair. In melanocytes may modulate both UV-B-induced cell cycle regulation and apoptosis.<ref>PMID:9822680</ref> <ref>PMID:9822679</ref> <ref>PMID:9564049</ref> <ref>PMID:10078208</ref> <ref>PMID:10660545</ref> <ref>PMID:15064730</ref> <ref>PMID:17611581</ref>

	==About this Structure==		==About this Structure==
Line 13:		Line 13:

	==Reference==		==Reference==
	<references group="xtra"/><references/>		<ref group="xtra">PMID:022179786</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Yang, W.]]		[[Category: Yang, W.]]

OCA at 09:59, 24 March 2013

2013-03-24T09:59:53Z

← Older revision		Revision as of 09:59, 24 March 2013
Line 1:		Line 1:
	~~'''Unreleased structure'''~~		{{STRUCTURE_3thy\| PDB=3thy \| SCENE= }}
			===Human MutSbeta complexed with an IDL of 2 bases (Loop2) and ADP===
			{{ABSTRACT_PUBMED_022179786}}

	The entry ~~3thy is ON HOLD~~ ~~until Paper Publication~~		==Disease==
			[[http://www.uniprot.org/uniprot/MSH2_HUMAN MSH2_HUMAN]] Defects in MSH2 are the cause of hereditary non-polyposis colorectal cancer type 1 (HNPCC1) [MIM:[http://omim.org/entry/120435 120435]]. Mutations in more than one gene locus can be involved alone or in combination in the production of the HNPCC phenotype (also called Lynch syndrome). Most families with clinically recognized HNPCC have mutations in either MLH1 or MSH2 genes. HNPCC is an autosomal, dominantly inherited disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early onset colorectal carcinoma (CRC) and extra-colonic cancers of the gastrointestinal, urological and female reproductive tracts. HNPCC is reported to be the most common form of inherited colorectal cancer in the Western world. Cancers in HNPCC originate within benign neoplastic polyps termed adenomas. Clinically, HNPCC is often divided into two subgroups. Type I: hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II: patients have an increased risk for cancers in certain tissues such as the uterus, ovary, breast, stomach, small intestine, skin, and larynx in addition to the colon. Diagnosis of classical HNPCC is based on the Amsterdam criteria: 3 or more relatives affected by colorectal cancer, one a first degree relative of the other two; 2 or more generation affected; 1 or more colorectal cancers presenting before 50 years of age; exclusion of hereditary polyposis syndromes. The term "suspected HNPCC" or "incomplete HNPCC" can be used to describe families who do not or only partially fulfill the Amsterdam criteria, but in whom a genetic basis for colon cancer is strongly suspected. MSH2 mutations may predispose to hematological malignancies and multiple cafe-au-lait spots.<ref>PMID:8261515</ref><ref>PMID:9889267</ref><ref>PMID:7874129</ref><ref>PMID:8872463</ref><ref>PMID:8700523</ref><ref>PMID:9311737</ref><ref>PMID:9240418</ref><ref>PMID:9419403</ref><ref>PMID:9048925</ref><ref>PMID:9298827</ref><ref>PMID:9718327</ref><ref>PMID:9559627</ref><ref>PMID:10375096</ref><ref>PMID:10573010</ref><ref>PMID:10386556</ref><ref>PMID:10528862</ref><ref>PMID:10777691</ref><ref>PMID:10612836</ref><ref>PMID:10829038</ref><ref>PMID:12132870</ref><ref>PMID:11726306</ref><ref>PMID:12373605</ref><ref>PMID:11920458</ref><ref>PMID:12124176</ref><ref>PMID:12112654</ref><ref>PMID:12200596</ref><ref>PMID:11870161</ref><ref>PMID:12362047</ref><ref>PMID:12658575</ref><ref>PMID:12655564</ref><ref>PMID:12655568</ref><ref>PMID:14635101</ref><ref>PMID:15046096</ref><ref>PMID:15300854</ref><ref>PMID:15365995</ref><ref>PMID:15613555</ref><ref>PMID:15342696</ref><ref>PMID:15896463</ref><ref>PMID:15996210</ref><ref>PMID:15870828</ref><ref>PMID:15991316</ref><ref>PMID:16451135</ref><ref>PMID:17101317</ref><ref>PMID:17128465</ref><ref>PMID:18625694</ref><ref>PMID:18951462</ref><ref>PMID:18561205</ref><ref>PMID:18781619</ref><ref>PMID:18822302</ref><ref>PMID:22102614</ref><ref>PMID:22371642</ref> Defects in MSH2 are a cause of Muir-Torre syndrome (MRTES) [MIM:[http://omim.org/entry/158320 158320]]. Rare autosomal dominant disorder characterized by sebaceous neoplasms and visceral malignancy.<ref>PMID:7713503</ref> Defects in MSH2 are a cause of susceptibility to endometrial cancer (ENDMC) [MIM:[http://omim.org/entry/608089 608089]].

	~~Authors~~: ~~Yang~~, W.		==Function==
			[[http://www.uniprot.org/uniprot/MSH2_HUMAN MSH2_HUMAN]] Component of the post-replicative DNA mismatch repair system (MMR). Forms two different heterodimers: MutS alpha (MSH2-MSH6 heterodimer) and MutS beta (MSH2-MSH3 heterodimer) which binds to DNA mismatches thereby initiating DNA repair. When bound, heterodimers bend the DNA helix and shields approximately 20 base pairs. MutS alpha recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. MutS beta recognizes larger insertion-deletion loops up to 13 nucleotides long. After mismatch binding, MutS alpha or beta forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis. ATP binding and hydrolysis play a pivotal role in mismatch repair functions. The ATPase activity associated with MutS alpha regulates binding similar to a molecular switch: mismatched DNA provokes ADP-->ATP exchange, resulting in a discernible conformational transition that converts MutS alpha into a sliding clamp capable of hydrolysis-independent diffusion along the DNA backbone. This transition is crucial for mismatch repair. MutS alpha may also play a role in DNA homologous recombination repair. In melanocytes may modulate both UV-B-induced cell cycle regulation and apoptosis.<ref>PMID:9822680</ref><ref>PMID:9822679</ref><ref>PMID:9564049</ref><ref>PMID:10078208</ref><ref>PMID:10660545</ref><ref>PMID:15064730</ref><ref>PMID:17611581</ref>

	~~Description~~: ~~Human MutSbeta complexed with an IDL of 2 bases (Loop2) and ADP~~		==About this Structure==
			[[3thy]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3THY OCA].

			==Reference==
			<references group="xtra"/><references/>
			[[Category: Homo sapiens]]
			[[Category: Yang, W.]]
			[[Category: Abc family atpase]]
			[[Category: Dna binding protein-dna complex]]
			[[Category: Mismatch recognition]]
			[[Category: Mismatched unpaired idl dna]]

OCA at 08:39, 30 October 2011

2011-10-30T08:39:53Z

← Older revision		Revision as of 08:39, 30 October 2011
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 3thy is ON HOLD		The entry 3thy is ON HOLD until Paper Publication

	Authors: Yang, W.		Authors: Yang, W.

	Description: Human MutSbeta complexed with an IDL of 2 bases (Loop2) and ADP		Description: Human MutSbeta complexed with an IDL of 2 bases (Loop2) and ADP

OCA: Protected "3thy" [edit=sysop:move=sysop]

2011-08-31T06:25:11Z

Protected "3thy" [edit=sysop:move=sysop]

← Older revision	Revision as of 06:25, 31 August 2011
(No difference)

OCA: New page: '''Unreleased structure''' The entry 3thy is ON HOLD Authors: Yang, W. Description: Human MutSbeta complexed with an IDL of 2 bases (Loop2) and ADP

2011-08-31T06:25:10Z

New page: '''Unreleased structure''' The entry 3thy is ON HOLD Authors: Yang, W. Description: Human MutSbeta complexed with an IDL of 2 bases (Loop2) and ADP

New page

'''Unreleased structure'''

The entry 3thy is ON HOLD

Authors: Yang, W.

Description: Human MutSbeta complexed with an IDL of 2 bases (Loop2) and ADP