OCA at 08:36, 9 May 2024

OCA — Thu, 09 May 2024 08:36:48 GMT

←Older revision		Revision as of 08:36, 9 May 2024
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-	'''Unreleased structure'''

-	~~The entry~~ 8tpv is ~~ON HOLD until Paper~~ Publication	+	==Structure of human hypoxanthine guanine phosphoribzosyltransferase in complex with [2S,4R]-4-Guanin-9-yl-2-(2-phosphonoethoxymethyl)-1-N-(3-phosphonopropionyl)pyrrolidine==
		+	<StructureSection load='8tpv' size='340' side='right'caption='[[8tpv]], [[Resolution\|resolution]] 2.27Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8tpv]] is a 4 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=8TPV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8TPV 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]] 2.27Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JEI:(3-{(2S,4R)-4-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)-2-[(2-phosphonoethoxy)methyl]pyrrolidin-1-yl}-3-oxopropyl)phosphonic+acid'>JEI</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=8tpv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8tpv OCA], [https://pdbe.org/8tpv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8tpv RCSB], [https://www.ebi.ac.uk/pdbsum/8tpv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8tpv ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[https://www.uniprot.org/uniprot/HPRT_HUMAN HPRT_HUMAN] Defects in HPRT1 are the cause of Lesch-Nyhan syndrome (LNS) [MIM:[https://omim.org/entry/300322 300322]. LNS is characterized by complete lack of enzymatic activity that results in hyperuricemia, choreoathetosis, mental retardation, and compulsive self-mutilation.<ref>PMID:6853716</ref> <ref>PMID:3384338</ref> <ref>PMID:3265398</ref> <ref>PMID:2910902</ref> <ref>PMID:2347587</ref> <ref>PMID:2358296</ref> <ref>PMID:2246854</ref> <ref>PMID:2071157</ref> <ref>PMID:7627191</ref> <ref>PMID:9452051</ref> Defects in HPRT1 are the cause of gout HPRT-related (GOUT-HPRT) [MIM:[https://omim.org/entry/300323 300323]; also known as HPRT-related gout or Kelley-Seegmiller syndrome. Gout is characterized by partial enzyme activity and hyperuricemia.<ref>PMID:6853490</ref> <ref>PMID:6572373</ref> <ref>PMID:6706936</ref> <ref>PMID:3358423</ref> <ref>PMID:3198771</ref> <ref>PMID:2909537</ref> [:]
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/HPRT_HUMAN HPRT_HUMAN] Converts guanine to guanosine monophosphate, and hypoxanthine to inosine monophosphate. Transfers the 5-phosphoribosyl group from 5-phosphoribosylpyrophosphate onto the purine. Plays a central role in the generation of purine nucleotides through the purine salvage pathway.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Inhibition of hypoxanthine-guanine-xanthine phosphoribosyltransferase activity decreases the pool of 6-oxo and 6-amino purine nucleoside monophosphates required for DNA and RNA synthesis, resulting in a reduction in cell growth. Therefore, inhibitors of this enzyme have potential to control infections, caused by Plasmodium falciparum and Plasmodium vivax, Trypanosoma brucei, Mycobacterium tuberculosis, and Helicobacter pylori. Five compounds synthesized here that contain a purine base covalently linked by a prolinol group to one or two phosphonate groups have K(i) values ranging from 3 nM to >10 muM, depending on the structure of the inhibitor and the biological origin of the enzyme. X-ray crystal structures show that, on binding, these prolinol-containing inhibitors stimulated the movement of active site loops in the enzyme. Against TBr in cell culture, a prodrug exhibited an EC(50) of 10 muM. Thus, these compounds are excellent candidates for further development as drug leads against infectious diseases as well as being potential anticancer agents.

-	~~Authors~~: Guddat, L.W.	+	Development of Prolinol Containing Inhibitors of Hypoxanthine-Guanine-Xanthine Phosphoribosyltransferase: Rational Structure-Based Drug Design.,Keough DT, Petrova M, King G, Kratochvil M, Pohl R, Dolezelova E, Zikova A, Guddat LW, Rejman D J Med Chem. 2024 Apr 23. doi: 10.1021/acs.jmedchem.4c00021. PMID:38651522<ref>PMID:38651522</ref>

-	~~Description: Structure of human hypoxanthine guanine phosphoribzosyltransferase in complex with [2S~~,~~4R]-4~~-~~Guanin~~-~~9-yl-2-(2-phosphonoethoxymethyl)-1-N-(3-phosphonopropionyl)pyrrolidine~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: Guddat~~, L.W~~]]	+	<div class="pdbe-citations 8tpv" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Guddat LW]]

OCA at 10:30, 6 March 2024

OCA — Wed, 06 Mar 2024 10:30:56 GMT

←Older revision		Revision as of 10:30, 6 March 2024
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Guddat, L.W.		Authors: Guddat, L.W.

OCA at 10:39, 1 February 2024

OCA — Thu, 01 Feb 2024 10:39:17 GMT

←Older revision		Revision as of 10:39, 1 February 2024
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Guddat, L.W.		Authors: Guddat, L.W.

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

OCA — Wed, 16 Aug 2023 06:57:13 GMT

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

←Older revision

Revision as of 06:57, 16 August 2023

OCA: New page: '''Unreleased structure''' The entry 8tpv is ON HOLD until sometime in the future Authors: Guddat, L.W. Description: Structure of human hypoxanthine guanine phosphoribzosyltransferase ...

OCA — Wed, 16 Aug 2023 06:57:12 GMT

New page: '''Unreleased structure''' The entry 8tpv is ON HOLD until sometime in the future Authors: Guddat, L.W. Description: Structure of human hypoxanthine guanine phosphoribzosyltransferase ...

New page

'''Unreleased structure'''

The entry 8tpv is ON HOLD until sometime in the future

Authors: Guddat, L.W.

Description: Structure of human hypoxanthine guanine phosphoribzosyltransferase in complex with [2S,4R]-4-Guanin-9-yl-2-(2-phosphonoethoxymethyl)-1-N-(3-phosphonopropionyl)pyrrolidine
[[Category: Unreleased Structures]]
[[Category: Guddat, L.W]]

8tpv - Revision history

OCA at 08:36, 9 May 2024

OCA at 10:30, 6 March 2024

OCA at 10:39, 1 February 2024

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

OCA: New page: '''Unreleased structure''' The entry 8tpv is ON HOLD until sometime in the future Authors: Guddat, L.W. Description: Structure of human hypoxanthine guanine phosphoribzosyltransferase ...