View source for 8omo


==DNA-unbound MutSbeta-ATP complex (bent clamp form)==
<StructureSection load='8omo' size='340' side='right'caption='[[8omo]], [[Resolution|resolution]] 3.43&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8omo]] is a 2 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=8OMO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8OMO FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.43&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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=8omo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8omo OCA], [https://pdbe.org/8omo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8omo RCSB], [https://www.ebi.ac.uk/pdbsum/8omo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8omo ProSAT]</span></td></tr>
</table>
== 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].
== 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> 
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Daub H]]
[[Category: Dominguez C]]
[[Category: Felsenfeld DP]]
[[Category: Finley M]]
[[Category: Haque T]]
[[Category: Iyer RR]]
[[Category: Lee J-H]]
[[Category: Monteagudo E]]
[[Category: Neudegger T]]
[[Category: Plotnikov N]]
[[Category: Prasad BC]]
[[Category: Steinbacher S]]
[[Category: Sztyler A]]
[[Category: Thieulin-Pardo G]]
[[Category: Thomsen M]]
[[Category: Vogt TF]]
[[Category: Wilkinson H]]