7rcb - Revision history

OCA at 09:26, 25 October 2023

2023-10-25T09:26:40Z

←Older revision		Revision as of 09:26, 25 October 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7rcb]] 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=7RCB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RCB FirstGlance]. <br>		<table><tr><td colspan='2'>[[7rcb]] 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=7RCB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RCB FirstGlance]. <br>
-	</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=7rcb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rcb OCA], [https://pdbe.org/7rcb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rcb RCSB], [https://www.ebi.ac.uk/pdbsum/7rcb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rcb ProSAT]</span></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]] 2Å</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=7rcb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rcb OCA], [https://pdbe.org/7rcb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rcb RCSB], [https://www.ebi.ac.uk/pdbsum/7rcb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rcb ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
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	==See Also==		==See Also==
	*[[DNA mismatch repair protein 3D structures\|DNA mismatch repair protein 3D structures]]		*[[DNA mismatch repair protein 3D structures\|DNA mismatch repair protein 3D structures]]
		+	*[[Endonuclease 3D structures\|Endonuclease 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 11:01, 30 November 2022

2022-11-30T11:01:43Z

←Older revision		Revision as of 11:01, 30 November 2022
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	==Crystal Structure of a PMS2 VUS==		==Crystal Structure of a PMS2 VUS==
-	<StructureSection load='7rcb' size='340' side='right'caption='[[7rcb]]' scene=''>	+	<StructureSection load='7rcb' size='340' side='right'caption='[[7rcb]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RCB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RCB FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7rcb]] 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=7RCB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RCB FirstGlance]. <br>
	</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=7rcb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rcb OCA], [https://pdbe.org/7rcb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rcb RCSB], [https://www.ebi.ac.uk/pdbsum/7rcb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rcb ProSAT]</span></td></tr>		</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=7rcb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rcb OCA], [https://pdbe.org/7rcb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rcb RCSB], [https://www.ebi.ac.uk/pdbsum/7rcb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rcb ProSAT]</span></td></tr>
	</table>		</table>
		+	== Disease ==
		+	[https://www.uniprot.org/uniprot/PMS2_HUMAN PMS2_HUMAN] Defects in PMS2 are the cause of hereditary non-polyposis colorectal cancer type 4 (HNPCC4) [MIM:[https://omim.org/entry/614337 614337]. 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, and accounts for 15% of all colon cancers. 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.<ref>PMID:15887124</ref> <ref>PMID:18178629</ref> Defects in PMS2 are a cause of mismatch repair cancer syndrome (MMRCS) [MIM:[https://omim.org/entry/276300 276300]; also known as Turcot syndrome or brain tumor-polyposis syndrome 1 (BTPS1). MMRCS is an autosomal dominant disorder characterized by malignant tumors of the brain associated with multiple colorectal adenomas. Skin features include sebaceous cysts, hyperpigmented and cafe au lait spots.<ref>PMID:7661930</ref> <ref>PMID:9419979</ref> <ref>PMID:15077197</ref> <ref>PMID:17557300</ref>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/PMS2_HUMAN PMS2_HUMAN] Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerizes with MLH1 to form MutL alpha. DNA repair is initiated by MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH6) binding to a dsDNA mismatch, then MutL alpha is recruited to the heteroduplex. Assembly of the MutL-MutS-heteroduplex ternary complex in presence of RFC and PCNA is sufficient to activate endonuclease activity of PMS2. It introduces single-strand breaks near the mismatch and thus generates new entry points for the exonuclease EXO1 to degrade the strand containing the mismatch. DNA methylation would prevent cleavage and therefore assure that only the newly mutated DNA strand is going to be corrected. MulL alpha (MLH1-PMS2) interacts physically with the clamp loader subunits of DNA polymerase III, suggesting that it may play a role to recruit the DNA polymerase III to the site of the MMR. Also implicated in DNA damage signaling, a process which induces cell cycle arrest and can lead to apoptosis in case of major DNA damages.<ref>PMID:16873062</ref> <ref>PMID:18206974</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Hereditary cancer syndromes account for approximately 5%-10% of all diagnosed cancer cases. Lynch syndrome (LS) is an autosomal dominant hereditary cancer condition that predisposes individuals to an elevated lifetime risk for developing colorectal, endometrial, and other cancers. LS results from a pathogenic mutation in one of four mismatch repair (MMR) genes (MSH2, MSH6, MLH1, and PMS2). The diagnosis of LS is often challenged by the identification of missense mutations, termed variants of uncertain significance, whose functional effect on the protein is not known. Of the eight PMS2 variants initially selected for this study, we identified a variant within the N-terminal domain where asparagine 335 is mutated to serine, p.Asn335Ser, which lacked ATPase activity, yet appears to be proficient in MMR. To expand our understanding of this functional dichotomy, we performed biophysical and structural studies, and noted that p.Asn335Ser binds to ATP but is unable to hydrolyze it to ADP. To examine the impact of p.Asn335Ser on MMR, we developed a novel in-cell fluorescent-based microsatellite instability reporter that revealed p.Asn335Ser maintained genomic stability. We conclude that in the absence of gross structural changes, PMS2 ATP hydrolysis is not necessary for proficient MMR and that the ATPase deficient p.Asn335Ser variant is likely benign.
		+
		+	PMS2 variant results in loss of ATPase activity without compromising mismatch repair.,D'Arcy BM, Arrington J, Weisman J, McClellan SB, Vandana, Yang Z, Deivanayagam C, Blount J, Prakash A Mol Genet Genomic Med. 2022 Feb 21:e1908. doi: 10.1002/mgg3.1908. PMID:35189042<ref>PMID:35189042</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7rcb" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[DNA mismatch repair protein 3D structures\|DNA mismatch repair protein 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: D'Arcy BM]]		[[Category: D'Arcy BM]]
	[[Category: Prakash A]]		[[Category: Prakash A]]

OCA at 06:21, 2 March 2022

2022-03-02T06:21:09Z

←Older revision		Revision as of 06:21, 2 March 2022
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-	'''Unreleased structure'''

-	~~The entry~~ 7rcb ~~is ON HOLD until Paper Publication~~	+	==Crystal Structure of a PMS2 VUS==
-		+	<StructureSection load='7rcb' size='340' side='right'caption='[[7rcb]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RCB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RCB FirstGlance]. <br>
-	~~Description~~:	+	</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=7rcb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rcb OCA], [https://pdbe.org/7rcb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rcb RCSB], [https://www.ebi.ac.uk/pdbsum/7rcb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rcb ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: D'Arcy BM]]
		+	[[Category: Prakash A]]

OCA at 07:59, 21 July 2021

2021-07-21T07:59:17Z

←Older revision		Revision as of 07:59, 21 July 2021
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7rcb is ON HOLD	+	The entry 7rcb is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7rcb" [edit=sysop:move=sysop]

2021-07-14T08:57:28Z

Protected "7rcb" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:57, 14 July 2021

OCA: New page: '''Unreleased structure''' The entry 7rcb is ON HOLD Authors: Description: Category: Unreleased Structures

2021-07-14T08:57:27Z

New page: '''Unreleased structure''' The entry 7rcb is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7rcb is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]