9da2 - Revision history

OCA at 19:32, 26 February 2025

2025-02-26T19:32:53Z

← Older revision		Revision as of 19:32, 26 February 2025
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	<table><tr><td colspan='2'>[[9da2]] 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=9DA2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9DA2 FirstGlance]. <br>		<table><tr><td colspan='2'>[[9da2]] 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=9DA2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9DA2 FirstGlance]. <br>
	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.13Å</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]] 1.13Å</td></tr>
	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1BBC:1-(2-~~deoxy-2~~-~~fluoro~~-5-~~O-phosphono-beta-D-arabinofuranosyl)-~~5-(hydroxymethyl)~~pyrimidine~~-2,4(~~1H,3H~~)-~~dione~~'>A1BBC</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1BBC:[(2~{R},3~{R},4~{S},5~{R})-4-fluoranyl-5-[5-(hydroxymethyl)-2,4-bis(oxidanylidene)pyrimidin-1-yl]-3-oxidanyl-oxolan-2-yl]methyl+dihydrogen+phosphate'>A1BBC</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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=9da2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9da2 OCA], [https://pdbe.org/9da2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9da2 RCSB], [https://www.ebi.ac.uk/pdbsum/9da2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9da2 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=9da2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9da2 OCA], [https://pdbe.org/9da2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9da2 RCSB], [https://www.ebi.ac.uk/pdbsum/9da2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9da2 ProSAT]</span></td></tr>
	</table>		</table>

OCA at 06:26, 5 February 2025

2025-02-05T06:26:47Z

← Older revision		Revision as of 06:26, 5 February 2025
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	~~'''Unreleased structure'''~~

	~~The entry~~ 9da2 is ~~ON HOLD until Paper~~ Publication		==Crystal structure of human DNPH1 bound to inhibitor 1b==
			<StructureSection load='9da2' size='340' side='right'caption='[[9da2]], [[Resolution\|resolution]] 1.13Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[9da2]] 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=9DA2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9DA2 FirstGlance]. <br>
			</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.13Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1BBC:1-(2-deoxy-2-fluoro-5-O-phosphono-beta-D-arabinofuranosyl)-5-(hydroxymethyl)pyrimidine-2,4(1H,3H)-dione'>A1BBC</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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=9da2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9da2 OCA], [https://pdbe.org/9da2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9da2 RCSB], [https://www.ebi.ac.uk/pdbsum/9da2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9da2 ProSAT]</span></td></tr>
			</table>
			== Function ==
			[https://www.uniprot.org/uniprot/DNPH1_HUMAN DNPH1_HUMAN] Catalyzes the cleavage of the N-glycosidic bond of deoxyribonucleoside 5'-monophosphates to yield deoxyribose 5-phosphate and a purine or pyrimidine base. Deoxyribonucleoside 5'-monophosphates containing purine bases are preferred to those containing pyrimidine bases (By similarity).[HAMAP-Rule:MF_03036]
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			DNPH1 is responsible for eliminating the epigenetically modified nucleotide, 5-hydroxymethyl-2'-deoxyuridine 5'-monophosphate (hmdUMP), preventing formation of hmdUTP, a mutation-inducing nucleotide. Loss of DNPH1 activity sensitizes PARP inhibition-resistant BRCA-deficient cancers by causing incorporation of hmdUTP into DNA. Hydrolysis of hmdUMP by DNPH1 proceeds through a covalent intermediate between Glu104 and 2-deoxyribose 5-phosphate, followed by hydrolysis, a reaction cycle with two transition states. We describe synthesis and characterization of transition state mimics for both transition states of DNPH1. Both transition states prefer inhibitors with cationic charge at the anomeric center and provide a foundation for inhibitor design. Ground-state complexes show reaction coordinate nucleophiles poised 3.3-3.7 A from the anomeric carbon while transition state analogs tighten the reaction coordinate to place the nucleophiles 2.7-2.8 A from the anomeric carbon. Crystal structures of DNPH1 with transition state analogs reveal transition states where the electrophilic ribocation migrates between the leaving groups and attacking nucleophiles.

	~~Authors:~~ Wagner, A~~.G.~~, ~~Schramm~~, ~~V.L.~~, Almo, S.C.~~, Ghosh, A~~.		Transition State Analogs of Human DNPH1 Reveal Two Electrophile Migration Mechanisms.,Wagner AG, Lang TBD, Ledingham ET, Ghosh A, Brooks D, Eskandari R, Suthagar K, Almo SC, Lamiable-Oulaidi F, Tyler PC, Schramm VL J Med Chem. 2025 Jan 16. doi: 10.1021/acs.jmedchem.4c02778. PMID:39818772<ref>PMID:39818772</ref>

	~~Description~~: ~~Crystal structure of human DNPH1 bound to inhibitor 1b~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	[[Category: ~~Unreleased~~ Structures]]		</div>
	[[Category: ~~Schramm, V.L~~]]		<div class="pdbe-citations 9da2" style="background-color:#fffaf0;"></div>
	[[Category: Ghosh, A]]		== References ==
	[[Category: ~~Wagner, A.G~~]]		<references/>
	[[Category: ~~Almo, S.C~~]]		__TOC__
			</StructureSection>
			[[Category: Homo sapiens]]
			[[Category: Large Structures]]
			[[Category: Almo SC]]
			[[Category: Ghosh A]]
			[[Category: Schramm VL]]
			[[Category: Wagner AG]]

OCA at 02:58, 17 October 2024

2024-10-17T02:58:09Z

← Older revision		Revision as of 02:58, 17 October 2024
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 9da2 is ON HOLD		The entry 9da2 is ON HOLD until Paper Publication

	Authors: Wagner, A.G., Schramm, V.L., Almo, S.C., Ghosh, A.		Authors: Wagner, A.G., Schramm, V.L., Almo, S.C., Ghosh, A.
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	Description: Crystal structure of human DNPH1 bound to inhibitor 1b		Description: Crystal structure of human DNPH1 bound to inhibitor 1b
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
			[[Category: Schramm, V.L]]
			[[Category: Ghosh, A]]
	[[Category: Wagner, A.G]]		[[Category: Wagner, A.G]]
	~~[[Category: Ghosh, A]]~~
	[[Category: Almo, S.C]]		[[Category: Almo, S.C]]
	~~[[Category: Schramm, V.L]]~~

OCA: Protected "9da2" [edit=sysop:move=sysop]

2024-08-28T04:16:58Z

Protected "9da2" [edit=sysop:move=sysop]

← Older revision	Revision as of 04:16, 28 August 2024
(No difference)

OCA: New page: '''Unreleased structure''' The entry 9da2 is ON HOLD Authors: Wagner, A.G., Schramm, V.L., Almo, S.C., Ghosh, A. Description: Crystal structure of human DNPH1 bound to inhibitor 1b [[C...

2024-08-28T04:16:57Z

New page: '''Unreleased structure''' The entry 9da2 is ON HOLD Authors: Wagner, A.G., Schramm, V.L., Almo, S.C., Ghosh, A. Description: Crystal structure of human DNPH1 bound to inhibitor 1b [[C...

New page

'''Unreleased structure'''

The entry 9da2 is ON HOLD

Authors: Wagner, A.G., Schramm, V.L., Almo, S.C., Ghosh, A.

Description: Crystal structure of human DNPH1 bound to inhibitor 1b
[[Category: Unreleased Structures]]
[[Category: Wagner, A.G]]
[[Category: Ghosh, A]]
[[Category: Almo, S.C]]
[[Category: Schramm, V.L]]