8ag6 - Revision history

OCA at 06:59, 8 February 2023

OCA — Wed, 08 Feb 2023 06:59:54 GMT

←Older revision		Revision as of 06:59, 8 February 2023
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	== 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>
		+
		+	==See Also==
		+	*[[DNA mismatch repair protein 3D structures\|DNA mismatch repair protein 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 06:34, 25 January 2023

OCA — Wed, 25 Jan 2023 06:34:23 GMT

←Older revision		Revision as of 06:34, 25 January 2023
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-	'''Unreleased structure'''

-	~~The entry~~ 8ag6 is ~~ON HOLD until Paper Publication~~	+	==human MutSalpha (MSH2/MSH6) binding to DNA with a GT mismatch==
-		+	<StructureSection load='8ag6' size='340' side='right'caption='[[8ag6]], [[Resolution\|resolution]] 2.80Å' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[8ag6]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8AG6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8AG6 FirstGlance]. <br>
-	~~Description~~:	+	</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>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8ag6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ag6 OCA], [https://pdbe.org/8ag6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ag6 RCSB], [https://www.ebi.ac.uk/pdbsum/8ag6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ag6 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: Synthetic construct]]
		+	[[Category: Bruekner SR]]
		+	[[Category: Sixma TK]]

OCA at 07:11, 14 December 2022

OCA — Wed, 14 Dec 2022 07:11:07 GMT

←Older revision		Revision as of 07:11, 14 December 2022
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8ag6 is ON HOLD	+	The entry 8ag6 is ON HOLD until Paper Publication

	Authors:		Authors:

OCA at 03:44, 18 August 2022

OCA — Thu, 18 Aug 2022 03:44:57 GMT

←Older revision		Revision as of 03:44, 18 August 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8ag6 is ON HOLD ~~until sometime in the future~~	+	The entry 8ag6 is ON HOLD

	Authors:		Authors:

OCA at 03:53, 10 August 2022

OCA — Wed, 10 Aug 2022 03:53:18 GMT

←Older revision		Revision as of 03:53, 10 August 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8ag6 is ON HOLD	+	The entry 8ag6 is ON HOLD until sometime in the future

	Authors:		Authors:

OCA: Protected "8ag6" [edit=sysop:move=sysop]

OCA — Wed, 27 Jul 2022 16:35:58 GMT

Protected "8ag6" [edit=sysop:move=sysop]

←Older revision

Revision as of 16:35, 27 July 2022

OCA: New page: '''Unreleased structure''' The entry 8ag6 is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 27 Jul 2022 16:35:57 GMT

New page: '''Unreleased structure''' The entry 8ag6 is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 8ag6 is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]