4eey - Revision history

OCA at 14:59, 14 March 2024

2024-03-14T14:59:47Z

←Older revision		Revision as of 14:59, 14 March 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4eey]] is a 3 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=4EEY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EEY FirstGlance]. <br>		<table><tr><td colspan='2'>[[4eey]] is a 3 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=4EEY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EEY FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CPT:CISPLATIN'>CPT</scene>, <scene name='pdbligand=DCP:2-DEOXYCYTIDINE-5-TRIPHOSPHATE'>DCP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 2.32Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CPT:CISPLATIN'>CPT</scene>, <scene name='pdbligand=DCP:2-DEOXYCYTIDINE-5-TRIPHOSPHATE'>DCP</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=4eey FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eey OCA], [https://pdbe.org/4eey PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4eey RCSB], [https://www.ebi.ac.uk/pdbsum/4eey PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4eey 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=4eey FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eey OCA], [https://pdbe.org/4eey PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4eey RCSB], [https://www.ebi.ac.uk/pdbsum/4eey PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4eey ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[https://www.uniprot.org/uniprot/POLH_HUMAN POLH_HUMAN]] Defects in POLH are the cause of xeroderma pigmentosum variant type (XPV) [MIM:[https://omim.org/entry/278750 278750]]; also designated as XP-V. Xeroderma pigmentosum (XP) is an autosomal recessive disease due to deficient nucleotide excision repair. It is characterized by hypersensitivity of the skin to sunlight, followed by high incidence of skin cancer and frequent neurologic abnormalities. XPV shows normal nucleotide excision repair, but an exaggerated delay in recovery of replicative DNA synthesis. Most XPV patients do not develop clinical symptoms and skin neoplasias until a later age. Clinical manifestations are limited to photo-induced deterioration of the skin and eyes.<ref>PMID:10385124</ref> <ref>PMID:10398605</ref> <ref>PMID:11032022</ref> <ref>PMID:11121129</ref> <ref>PMID:11773631</ref>	+	[https://www.uniprot.org/uniprot/POLH_HUMAN POLH_HUMAN] Defects in POLH are the cause of xeroderma pigmentosum variant type (XPV) [MIM:[https://omim.org/entry/278750 278750]; also designated as XP-V. Xeroderma pigmentosum (XP) is an autosomal recessive disease due to deficient nucleotide excision repair. It is characterized by hypersensitivity of the skin to sunlight, followed by high incidence of skin cancer and frequent neurologic abnormalities. XPV shows normal nucleotide excision repair, but an exaggerated delay in recovery of replicative DNA synthesis. Most XPV patients do not develop clinical symptoms and skin neoplasias until a later age. Clinical manifestations are limited to photo-induced deterioration of the skin and eyes.<ref>PMID:10385124</ref> <ref>PMID:10398605</ref> <ref>PMID:11032022</ref> <ref>PMID:11121129</ref> <ref>PMID:11773631</ref>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/POLH_HUMAN POLH_HUMAN]] DNA polymerase specifically involved in DNA repair. Plays an important role in translesion synthesis, where the normal high fidelity DNA polymerases cannot proceed and DNA synthesis stalls. Plays an important role in the repair of UV-induced pyrimidine dimers. Depending on the context, it inserts the correct base, but causes frequent base transitions and transversions. May play a role in hypermutation at immunoglobulin genes. Forms a Schiff base with 5'-deoxyribose phosphate at abasic sites, but does not have lyase activity. Targets POLI to replication foci.<ref>PMID:10385124</ref> <ref>PMID:11743006</ref> <ref>PMID:11376341</ref> <ref>PMID:14630940</ref> <ref>PMID:14734526</ref>	+	[https://www.uniprot.org/uniprot/POLH_HUMAN POLH_HUMAN] DNA polymerase specifically involved in DNA repair. Plays an important role in translesion synthesis, where the normal high fidelity DNA polymerases cannot proceed and DNA synthesis stalls. Plays an important role in the repair of UV-induced pyrimidine dimers. Depending on the context, it inserts the correct base, but causes frequent base transitions and transversions. May play a role in hypermutation at immunoglobulin genes. Forms a Schiff base with 5'-deoxyribose phosphate at abasic sites, but does not have lyase activity. Targets POLI to replication foci.<ref>PMID:10385124</ref> <ref>PMID:11743006</ref> <ref>PMID:11376341</ref> <ref>PMID:14630940</ref> <ref>PMID:14734526</ref>
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	A major clinical problem in the use of cisplatin to treat cancers is tumor resistance. DNA polymerase eta (Pol-eta) is a crucial polymerase that allows cancer cells to cope with the cisplatin-DNA adducts that are formed during chemotherapy. We present here a structure of human Pol-eta inserting deoxycytidine triphosphate (dCTP) opposite a cisplatin intrastrand cross-link (PtGpG). We show that the specificity of human Pol-eta for PtGpG derives from an active site that is open to permit Watson-Crick geometry of the nascent PtGpG-dCTP base pair and to accommodate the lesion without steric hindrance. This specificity is augmented by the residues Gln38 and Ser62, which interact with PtGpG, and Arg61, which interacts with the incoming dCTP. Collectively, the structure provides a basis for understanding how Pol-eta in human cells can tolerate the DNA damage caused by cisplatin chemotherapy and offers a framework for the design of inhibitors in cancer therapy.	+

-	Structural basis for cisplatin DNA damage tolerance by human polymerase eta during cancer chemotherapy.,Ummat A, Rechkoblit O, Jain R, Roy Choudhury J, Johnson RE, Silverstein TD, Buku A, Lone S, Prakash L, Prakash S, Aggarwal AK Nat Struct Mol Biol. 2012 May 6;19(6):628-32. doi: 10.1038/nsmb.2295. PMID:22562137<ref>PMID:22562137</ref>	+	==See Also==
-		+	*[[DNA polymerase 3D structures\|DNA polymerase 3D structures]]
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class~~=~~"pdbe-citations 4eey" style~~=~~"background-color:#fffaf0;"></div>~~	+
	== References ==		== References ==
	<references/>		<references/>

OCA at 07:08, 28 September 2022

2022-09-28T07:08:14Z

←Older revision		Revision as of 07:08, 28 September 2022
Line 1:		Line 1:

	==Crystal structure of human DNA polymerase eta in ternary complex with a cisplatin DNA adduct==		==Crystal structure of human DNA polymerase eta in ternary complex with a cisplatin DNA adduct==
-	<StructureSection load='4eey' size='340' side='right' caption='[[4eey]], [[Resolution\|resolution]] 2.32Å' scene=''>	+	<StructureSection load='4eey' size='340' side='right'caption='[[4eey]], [[Resolution\|resolution]] 2.32Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4eey]] is a 3 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=4EEY OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4EEY FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4eey]] is a 3 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=4EEY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EEY FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CPT:CISPLATIN'>CPT</scene>, <scene name='pdbligand=DCP:2-DEOXYCYTIDINE-5-TRIPHOSPHATE'>DCP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CPT:CISPLATIN'>CPT</scene>, <scene name='pdbligand=DCP:2-DEOXYCYTIDINE-5-TRIPHOSPHATE'>DCP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">POLH, RAD30, RAD30A, XPV ([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'>[https://proteopedia.org/fgij/fg.htm?mol=4eey FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eey OCA], [https://pdbe.org/4eey PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4eey RCSB], [https://www.ebi.ac.uk/pdbsum/4eey PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4eey ProSAT]</span></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA-directed_DNA_polymerase DNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.7 2.7.7.7] </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=4eey FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eey OCA], [~~http~~://pdbe.org/4eey PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4eey RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4eey PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4eey ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[[~~http~~://www.uniprot.org/uniprot/POLH_HUMAN POLH_HUMAN]] Defects in POLH are the cause of xeroderma pigmentosum variant type (XPV) [MIM:[~~http~~://omim.org/entry/278750 278750]]; also designated as XP-V. Xeroderma pigmentosum (XP) is an autosomal recessive disease due to deficient nucleotide excision repair. It is characterized by hypersensitivity of the skin to sunlight, followed by high incidence of skin cancer and frequent neurologic abnormalities. XPV shows normal nucleotide excision repair, but an exaggerated delay in recovery of replicative DNA synthesis. Most XPV patients do not develop clinical symptoms and skin neoplasias until a later age. Clinical manifestations are limited to photo-induced deterioration of the skin and eyes.<ref>PMID:10385124</ref> <ref>PMID:10398605</ref> <ref>PMID:11032022</ref> <ref>PMID:11121129</ref> <ref>PMID:11773631</ref>	+	[[https://www.uniprot.org/uniprot/POLH_HUMAN POLH_HUMAN]] Defects in POLH are the cause of xeroderma pigmentosum variant type (XPV) [MIM:[https://omim.org/entry/278750 278750]]; also designated as XP-V. Xeroderma pigmentosum (XP) is an autosomal recessive disease due to deficient nucleotide excision repair. It is characterized by hypersensitivity of the skin to sunlight, followed by high incidence of skin cancer and frequent neurologic abnormalities. XPV shows normal nucleotide excision repair, but an exaggerated delay in recovery of replicative DNA synthesis. Most XPV patients do not develop clinical symptoms and skin neoplasias until a later age. Clinical manifestations are limited to photo-induced deterioration of the skin and eyes.<ref>PMID:10385124</ref> <ref>PMID:10398605</ref> <ref>PMID:11032022</ref> <ref>PMID:11121129</ref> <ref>PMID:11773631</ref>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/POLH_HUMAN POLH_HUMAN]] DNA polymerase specifically involved in DNA repair. Plays an important role in translesion synthesis, where the normal high fidelity DNA polymerases cannot proceed and DNA synthesis stalls. Plays an important role in the repair of UV-induced pyrimidine dimers. Depending on the context, it inserts the correct base, but causes frequent base transitions and transversions. May play a role in hypermutation at immunoglobulin genes. Forms a Schiff base with 5'-deoxyribose phosphate at abasic sites, but does not have lyase activity. Targets POLI to replication foci.<ref>PMID:10385124</ref> <ref>PMID:11743006</ref> <ref>PMID:11376341</ref> <ref>PMID:14630940</ref> <ref>PMID:14734526</ref>	+	[[https://www.uniprot.org/uniprot/POLH_HUMAN POLH_HUMAN]] DNA polymerase specifically involved in DNA repair. Plays an important role in translesion synthesis, where the normal high fidelity DNA polymerases cannot proceed and DNA synthesis stalls. Plays an important role in the repair of UV-induced pyrimidine dimers. Depending on the context, it inserts the correct base, but causes frequent base transitions and transversions. May play a role in hypermutation at immunoglobulin genes. Forms a Schiff base with 5'-deoxyribose phosphate at abasic sites, but does not have lyase activity. Targets POLI to replication foci.<ref>PMID:10385124</ref> <ref>PMID:11743006</ref> <ref>PMID:11376341</ref> <ref>PMID:14630940</ref> <ref>PMID:14734526</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 4eey" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4eey" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[DNA polymerase\|DNA polymerase]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~DNA-directed DNA polymerase~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Human~~]]	+	[[Category: Large Structures]]
-	[[Category: Aggarwal~~, A K~~]]	+	[[Category: Aggarwal AK]]
-	[[Category: Buku, A]]	+	[[Category: Buku A]]
-	[[Category: Choudhury~~, J R~~]]	+	[[Category: Choudhury JR]]
-	[[Category: Jain, R]]	+	[[Category: Jain R]]
-	[[Category: Johnson~~, R E~~]]	+	[[Category: Johnson RE]]
-	[[Category: Lone, S]]	+	[[Category: Lone S]]
-	[[Category: Prakash, L]]	+	[[Category: Prakash L]]
-	[[Category: Prakash, S]]	+	[[Category: Prakash S]]
-	[[Category: Rechkoblit, O]]	+	[[Category: Rechkoblit O]]
-	[[Category: Silverstein~~, T D~~]]	+	[[Category: Silverstein TD]]
-	[[Category: Ummat, A]]	+	[[Category: Ummat A]]
-	~~[[Category: Dna repair]]~~	+
-	~~[[Category: Dna replication]]~~	+
-	~~[[Category: Transferase-dna complex~~]]	+

OCA at 17:23, 11 August 2016

2016-08-11T17:23:01Z

←Older revision		Revision as of 17:23, 11 August 2016
Line 1:		Line 1:
		+
	==Crystal structure of human DNA polymerase eta in ternary complex with a cisplatin DNA adduct==		==Crystal structure of human DNA polymerase eta in ternary complex with a cisplatin DNA adduct==
	<StructureSection load='4eey' size='340' side='right' caption='[[4eey]], [[Resolution\|resolution]] 2.32Å' scene=''>		<StructureSection load='4eey' size='340' side='right' caption='[[4eey]], [[Resolution\|resolution]] 2.32Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4eey]] is a 3 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=4EEY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EEY FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4eey]] is a 3 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=4EEY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EEY FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CPT:CISPLATIN'>CPT</scene>, <scene name='pdbligand=DCP:2-DEOXYCYTIDINE-5-TRIPHOSPHATE'>DCP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CPT:CISPLATIN'>CPT</scene>, <scene name='pdbligand=DCP:2-DEOXYCYTIDINE-5-TRIPHOSPHATE'>DCP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">POLH, RAD30, RAD30A, XPV ([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">POLH, RAD30, RAD30A, XPV ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA-directed_DNA_polymerase DNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.7 2.7.7.7] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA-directed_DNA_polymerase DNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.7 2.7.7.7] </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=4eey FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eey OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4eey RCSB], [http://www.ebi.ac.uk/pdbsum/4eey 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=4eey FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eey OCA], [http://pdbe.org/4eey PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4eey RCSB], [http://www.ebi.ac.uk/pdbsum/4eey PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4eey 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 4eey" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 28:		Line 30:
	</StructureSection>		</StructureSection>
	[[Category: DNA-directed DNA polymerase]]		[[Category: DNA-directed DNA polymerase]]
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Aggarwal, A K]]		[[Category: Aggarwal, A K]]
	[[Category: Buku, A]]		[[Category: Buku, A]]

OCA at 14:16, 4 January 2015

2015-01-04T14:16:07Z

←Older revision		Revision as of 14:16, 4 January 2015
Line 1:		Line 1:
-	~~{{STRUCTURE_4eey\| PDB=4eey \| SCENE= }}~~	+	==Crystal structure of human DNA polymerase eta in ternary complex with a cisplatin DNA adduct==
-	===Crystal structure of human DNA polymerase eta in ternary complex with a cisplatin DNA adduct===	+	<StructureSection load='4eey' size='340' side='right' caption='[[4eey]], [[Resolution\|resolution]] 2.32Å' scene=''>
-	~~{{ABSTRACT_PUBMED_22562137}}~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4eey]] is a 3 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=4EEY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EEY FirstGlance]. <br>
-	==Disease==	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CPT:CISPLATIN'>CPT</scene>, <scene name='pdbligand=DCP:2-DEOXYCYTIDINE-5-TRIPHOSPHATE'>DCP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">POLH, RAD30, RAD30A, XPV ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA-directed_DNA_polymerase DNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.7 2.7.7.7] </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=4eey FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eey OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4eey RCSB], [http://www.ebi.ac.uk/pdbsum/4eey PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
	[[http://www.uniprot.org/uniprot/POLH_HUMAN POLH_HUMAN]] Defects in POLH are the cause of xeroderma pigmentosum variant type (XPV) [MIM:[http://omim.org/entry/278750 278750]]; also designated as XP-V. Xeroderma pigmentosum (XP) is an autosomal recessive disease due to deficient nucleotide excision repair. It is characterized by hypersensitivity of the skin to sunlight, followed by high incidence of skin cancer and frequent neurologic abnormalities. XPV shows normal nucleotide excision repair, but an exaggerated delay in recovery of replicative DNA synthesis. Most XPV patients do not develop clinical symptoms and skin neoplasias until a later age. Clinical manifestations are limited to photo-induced deterioration of the skin and eyes.<ref>PMID:10385124</ref> <ref>PMID:10398605</ref> <ref>PMID:11032022</ref> <ref>PMID:11121129</ref> <ref>PMID:11773631</ref>		[[http://www.uniprot.org/uniprot/POLH_HUMAN POLH_HUMAN]] Defects in POLH are the cause of xeroderma pigmentosum variant type (XPV) [MIM:[http://omim.org/entry/278750 278750]]; also designated as XP-V. Xeroderma pigmentosum (XP) is an autosomal recessive disease due to deficient nucleotide excision repair. It is characterized by hypersensitivity of the skin to sunlight, followed by high incidence of skin cancer and frequent neurologic abnormalities. XPV shows normal nucleotide excision repair, but an exaggerated delay in recovery of replicative DNA synthesis. Most XPV patients do not develop clinical symptoms and skin neoplasias until a later age. Clinical manifestations are limited to photo-induced deterioration of the skin and eyes.<ref>PMID:10385124</ref> <ref>PMID:10398605</ref> <ref>PMID:11032022</ref> <ref>PMID:11121129</ref> <ref>PMID:11773631</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/POLH_HUMAN POLH_HUMAN]] DNA polymerase specifically involved in DNA repair. Plays an important role in translesion synthesis, where the normal high fidelity DNA polymerases cannot proceed and DNA synthesis stalls. Plays an important role in the repair of UV-induced pyrimidine dimers. Depending on the context, it inserts the correct base, but causes frequent base transitions and transversions. May play a role in hypermutation at immunoglobulin genes. Forms a Schiff base with 5'-deoxyribose phosphate at abasic sites, but does not have lyase activity. Targets POLI to replication foci.<ref>PMID:10385124</ref> <ref>PMID:11743006</ref> <ref>PMID:11376341</ref> <ref>PMID:14630940</ref> <ref>PMID:14734526</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	A major clinical problem in the use of cisplatin to treat cancers is tumor resistance. DNA polymerase eta (Pol-eta) is a crucial polymerase that allows cancer cells to cope with the cisplatin-DNA adducts that are formed during chemotherapy. We present here a structure of human Pol-eta inserting deoxycytidine triphosphate (dCTP) opposite a cisplatin intrastrand cross-link (PtGpG). We show that the specificity of human Pol-eta for PtGpG derives from an active site that is open to permit Watson-Crick geometry of the nascent PtGpG-dCTP base pair and to accommodate the lesion without steric hindrance. This specificity is augmented by the residues Gln38 and Ser62, which interact with PtGpG, and Arg61, which interacts with the incoming dCTP. Collectively, the structure provides a basis for understanding how Pol-eta in human cells can tolerate the DNA damage caused by cisplatin chemotherapy and offers a framework for the design of inhibitors in cancer therapy.

-	~~==Function==~~	+	Structural basis for cisplatin DNA damage tolerance by human polymerase eta during cancer chemotherapy.,Ummat A, Rechkoblit O, Jain R, Roy Choudhury J, Johnson RE, Silverstein TD, Buku A, Lone S, Prakash L, Prakash S, Aggarwal AK Nat Struct Mol Biol. 2012 May 6;19(6):628-32. doi: 10.1038/nsmb.2295. PMID:22562137<ref>PMID:22562137</ref>
-	~~[[http://www.uniprot.org/uniprot/POLH_HUMAN POLH_HUMAN]]~~ DNA polymerase ~~specifically involved in DNA repair~~. ~~Plays an important role in translesion synthesis~~, ~~where the normal high fidelity DNA polymerases cannot proceed and DNA synthesis stalls. Plays an important role in the repair of UV-induced pyrimidine dimers. Depending on the context~~, ~~it inserts the correct base~~, ~~but causes frequent base transitions and transversions~~. May ~~play a role in hypermutation at immunoglobulin genes. Forms a Schiff base with 5'~~-~~deoxyribose phosphate at abasic sites, but does not have lyase activity~~. ~~Targets POLI to replication foci~~.~~<ref>PMID:10385124<~~/~~ref> <ref>~~PMID:~~11743006</ref> <ref>PMID:11376341</ref> <ref>PMID:14630940</ref>~~ <ref>PMID:~~14734526~~</ref>	+

-	~~==About this Structure==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[4eey]] is~~ a ~~3 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=4EEY OCA].~~	+	</div>

-	==~~Reference~~==	+	==See Also==
-	~~<ref group~~=~~"xtra">PMID:022562137</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	*[[DNA polymerase\|DNA polymerase]]
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: DNA-directed DNA polymerase]]		[[Category: DNA-directed DNA polymerase]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Aggarwal, A K.]]	+	[[Category: Aggarwal, A K]]
-	[[Category: Buku, A.]]	+	[[Category: Buku, A]]
-	[[Category: Choudhury, J R.]]	+	[[Category: Choudhury, J R]]
-	[[Category: Jain, R.]]	+	[[Category: Jain, R]]
-	[[Category: Johnson, R E.]]	+	[[Category: Johnson, R E]]
-	[[Category: Lone, S.]]	+	[[Category: Lone, S]]
-	[[Category: Prakash, L.]]	+	[[Category: Prakash, L]]
-	[[Category: Prakash, S.]]	+	[[Category: Prakash, S]]
-	[[Category: Rechkoblit, O.]]	+	[[Category: Rechkoblit, O]]
-	[[Category: Silverstein, T D.]]	+	[[Category: Silverstein, T D]]
-	[[Category: Ummat, A.]]	+	[[Category: Ummat, A]]
	[[Category: Dna repair]]		[[Category: Dna repair]]
	[[Category: Dna replication]]		[[Category: Dna replication]]
	[[Category: Transferase-dna complex]]		[[Category: Transferase-dna complex]]

OCA at 08:52, 19 June 2013

2013-06-19T08:52:49Z

←Older revision		Revision as of 08:52, 19 June 2013
Line 1:		Line 1:
	{{STRUCTURE_4eey\| PDB=4eey \| SCENE= }}		{{STRUCTURE_4eey\| PDB=4eey \| SCENE= }}
	===Crystal structure of human DNA polymerase eta in ternary complex with a cisplatin DNA adduct===		===Crystal structure of human DNA polymerase eta in ternary complex with a cisplatin DNA adduct===
		+	{{ABSTRACT_PUBMED_22562137}}

	==Disease==		==Disease==
-	[[http://www.uniprot.org/uniprot/POLH_HUMAN POLH_HUMAN]] Defects in POLH are the cause of xeroderma pigmentosum variant type (XPV) [MIM:[http://omim.org/entry/278750 278750]]; also designated as XP-V. Xeroderma pigmentosum (XP) is an autosomal recessive disease due to deficient nucleotide excision repair. It is characterized by hypersensitivity of the skin to sunlight, followed by high incidence of skin cancer and frequent neurologic abnormalities. XPV shows normal nucleotide excision repair, but an exaggerated delay in recovery of replicative DNA synthesis. Most XPV patients do not develop clinical symptoms and skin neoplasias until a later age. Clinical manifestations are limited to photo-induced deterioration of the skin and eyes.<ref>PMID:10385124</ref><ref>PMID:10398605</ref><ref>PMID:11032022</ref><ref>PMID:11121129</ref><ref>PMID:11773631</ref>	+	[[http://www.uniprot.org/uniprot/POLH_HUMAN POLH_HUMAN]] Defects in POLH are the cause of xeroderma pigmentosum variant type (XPV) [MIM:[http://omim.org/entry/278750 278750]]; also designated as XP-V. Xeroderma pigmentosum (XP) is an autosomal recessive disease due to deficient nucleotide excision repair. It is characterized by hypersensitivity of the skin to sunlight, followed by high incidence of skin cancer and frequent neurologic abnormalities. XPV shows normal nucleotide excision repair, but an exaggerated delay in recovery of replicative DNA synthesis. Most XPV patients do not develop clinical symptoms and skin neoplasias until a later age. Clinical manifestations are limited to photo-induced deterioration of the skin and eyes.<ref>PMID:10385124</ref> <ref>PMID:10398605</ref> <ref>PMID:11032022</ref> <ref>PMID:11121129</ref> <ref>PMID:11773631</ref>

	==Function==		==Function==
-	[[http://www.uniprot.org/uniprot/POLH_HUMAN POLH_HUMAN]] DNA polymerase specifically involved in DNA repair. Plays an important role in translesion synthesis, where the normal high fidelity DNA polymerases cannot proceed and DNA synthesis stalls. Plays an important role in the repair of UV-induced pyrimidine dimers. Depending on the context, it inserts the correct base, but causes frequent base transitions and transversions. May play a role in hypermutation at immunoglobulin genes. Forms a Schiff base with 5'-deoxyribose phosphate at abasic sites, but does not have lyase activity. Targets POLI to replication foci.<ref>PMID:10385124</ref><ref>PMID:11743006</ref><ref>PMID:11376341</ref><ref>PMID:14630940</ref><ref>PMID:14734526</ref>	+	[[http://www.uniprot.org/uniprot/POLH_HUMAN POLH_HUMAN]] DNA polymerase specifically involved in DNA repair. Plays an important role in translesion synthesis, where the normal high fidelity DNA polymerases cannot proceed and DNA synthesis stalls. Plays an important role in the repair of UV-induced pyrimidine dimers. Depending on the context, it inserts the correct base, but causes frequent base transitions and transversions. May play a role in hypermutation at immunoglobulin genes. Forms a Schiff base with 5'-deoxyribose phosphate at abasic sites, but does not have lyase activity. Targets POLI to replication foci.<ref>PMID:10385124</ref> <ref>PMID:11743006</ref> <ref>PMID:11376341</ref> <ref>PMID:14630940</ref> <ref>PMID:14734526</ref>

	==About this Structure==		==About this Structure==
	[[4eey]] is a 3 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=4EEY OCA].		[[4eey]] is a 3 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=4EEY OCA].
-
-	==See Also==
-	*[[DNA polymerase\|DNA polymerase]]

	==Reference==		==Reference==
-	<references group="xtra"/><references/>	+	<ref group="xtra">PMID:022562137</ref><references group="xtra"/><references/>
	[[Category: DNA-directed DNA polymerase]]		[[Category: DNA-directed DNA polymerase]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]

OCA at 02:47, 25 March 2013

2013-03-25T02:47:38Z

←Older revision		Revision as of 02:47, 25 March 2013
Line 1:		Line 1:
-	[[Image:4eey.png\|left\|200px]]
-
	{{STRUCTURE_4eey\| PDB=4eey \| SCENE= }}		{{STRUCTURE_4eey\| PDB=4eey \| SCENE= }}
-
	===Crystal structure of human DNA polymerase eta in ternary complex with a cisplatin DNA adduct===		===Crystal structure of human DNA polymerase eta in ternary complex with a cisplatin DNA adduct===

		+	==Disease==
		+	[[http://www.uniprot.org/uniprot/POLH_HUMAN POLH_HUMAN]] Defects in POLH are the cause of xeroderma pigmentosum variant type (XPV) [MIM:[http://omim.org/entry/278750 278750]]; also designated as XP-V. Xeroderma pigmentosum (XP) is an autosomal recessive disease due to deficient nucleotide excision repair. It is characterized by hypersensitivity of the skin to sunlight, followed by high incidence of skin cancer and frequent neurologic abnormalities. XPV shows normal nucleotide excision repair, but an exaggerated delay in recovery of replicative DNA synthesis. Most XPV patients do not develop clinical symptoms and skin neoplasias until a later age. Clinical manifestations are limited to photo-induced deterioration of the skin and eyes.<ref>PMID:10385124</ref><ref>PMID:10398605</ref><ref>PMID:11032022</ref><ref>PMID:11121129</ref><ref>PMID:11773631</ref>
		+
		+	==Function==
		+	[[http://www.uniprot.org/uniprot/POLH_HUMAN POLH_HUMAN]] DNA polymerase specifically involved in DNA repair. Plays an important role in translesion synthesis, where the normal high fidelity DNA polymerases cannot proceed and DNA synthesis stalls. Plays an important role in the repair of UV-induced pyrimidine dimers. Depending on the context, it inserts the correct base, but causes frequent base transitions and transversions. May play a role in hypermutation at immunoglobulin genes. Forms a Schiff base with 5'-deoxyribose phosphate at abasic sites, but does not have lyase activity. Targets POLI to replication foci.<ref>PMID:10385124</ref><ref>PMID:11743006</ref><ref>PMID:11376341</ref><ref>PMID:14630940</ref><ref>PMID:14734526</ref>

	==About this Structure==		==About this Structure==
Line 11:		Line 13:
	==See Also==		==See Also==
	*[[DNA polymerase\|DNA polymerase]]		*[[DNA polymerase\|DNA polymerase]]
		+
		+	==Reference==
		+	<references group="xtra"/><references/>
	[[Category: DNA-directed DNA polymerase]]		[[Category: DNA-directed DNA polymerase]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]

OCA at 08:25, 20 October 2012

2012-10-20T08:25:37Z

←Older revision		Revision as of 08:25, 20 October 2012
Line 7:		Line 7:

	==About this Structure==		==About this Structure==
-	[[4eey]] is a 3 chain structure ~~of [[DNA polymerase]]~~ 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=4EEY OCA].	+	[[4eey]] is a 3 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=4EEY OCA].

	==See Also==		==See Also==

OCA at 19:28, 25 July 2012

2012-07-25T19:28:52Z

←Older revision		Revision as of 19:28, 25 July 2012
Line 1:		Line 1:
-	[[Image:4eey.~~jpg~~\|left\|200px]]	+	[[Image:4eey.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_4eey", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_4eey\| PDB=4eey \| SCENE= }}		{{STRUCTURE_4eey\| PDB=4eey \| SCENE= }}

Line 13:		Line 7:

	==About this Structure==		==About this Structure==
-	[[4eey]] is a 3 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=4EEY OCA].	+	[[4eey]] is a 3 chain structure of [[DNA polymerase]] 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=4EEY OCA].
		+
		+	==See Also==
		+	*[[DNA polymerase\|DNA polymerase]]
	[[Category: DNA-directed DNA polymerase]]		[[Category: DNA-directed DNA polymerase]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]

OCA at 09:26, 9 May 2012

2012-05-09T09:26:37Z

←Older revision		Revision as of 09:26, 9 May 2012
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:4eey.jpg\|left\|200px]]

-	The ~~entry 4eey~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_4eey", creates the "Structure Box" on the page.
		+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
		+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
		+	or leave the SCENE parameter empty for the default display.
		+	-->
		+	{{STRUCTURE_4eey\| PDB=4eey \| SCENE= }}

-	~~Authors: Ummat, A., Rechkoblit, O., Jain, R., Choudhury, J.R., Johnson, R.E., Silverstein, T.D., Buku, A., Lone, S., Prakash, L., Prakash, S., Aggarwal, A.K.~~	+	===Crystal structure of human DNA polymerase eta in ternary complex with a cisplatin DNA adduct===

-	~~Description: Crystal~~ structure ~~of human~~ DNA polymerase ~~eta in ternary~~ complex ~~with a cisplatin DNA adduct~~	+
		+	==About this Structure==
		+	[[4eey]] is a 3 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=4EEY OCA].
		+	[[Category: DNA-directed DNA polymerase]]
		+	[[Category: Homo sapiens]]
		+	[[Category: Aggarwal, A K.]]
		+	[[Category: Buku, A.]]
		+	[[Category: Choudhury, J R.]]
		+	[[Category: Jain, R.]]
		+	[[Category: Johnson, R E.]]
		+	[[Category: Lone, S.]]
		+	[[Category: Prakash, L.]]
		+	[[Category: Prakash, S.]]
		+	[[Category: Rechkoblit, O.]]
		+	[[Category: Silverstein, T D.]]
		+	[[Category: Ummat, A.]]
		+	[[Category: Dna repair]]
		+	[[Category: Dna replication]]
		+	[[Category: Transferase-dna complex]]

OCA at 07:30, 18 April 2012

2012-04-18T07:30:56Z

←Older revision		Revision as of 07:30, 18 April 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4eey is ON HOLD	+	The entry 4eey is ON HOLD until Paper Publication

	Authors: Ummat, A., Rechkoblit, O., Jain, R., Choudhury, J.R., Johnson, R.E., Silverstein, T.D., Buku, A., Lone, S., Prakash, L., Prakash, S., Aggarwal, A.K.		Authors: Ummat, A., Rechkoblit, O., Jain, R., Choudhury, J.R., Johnson, R.E., Silverstein, T.D., Buku, A., Lone, S., Prakash, L., Prakash, S., Aggarwal, A.K.

	Description: Crystal structure of human DNA polymerase eta in ternary complex with a cisplatin DNA adduct		Description: Crystal structure of human DNA polymerase eta in ternary complex with a cisplatin DNA adduct