OCA at 08:37, 9 May 2024

OCA — Thu, 09 May 2024 08:37:00 GMT

←Older revision		Revision as of 08:37, 9 May 2024
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-	'''Unreleased structure'''

-	~~The entry~~ 8ts4 is ~~ON HOLD until Paper~~ Publication	+	==Crystal structure of T. Brucei hypoxanthine guanine phosphoribosyltransferase in complex with [2S,4S]-4-Guanin-9-yl-2-(2-phosphonoethoxymethyl)-1-N-(3-phosphonopropionyl)pyrrolidine==
		+	<StructureSection load='8ts4' size='340' side='right'caption='[[8ts4]], [[Resolution\|resolution]] 2.20Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8ts4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_brucei Trypanosoma brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8TS4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8TS4 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]] 2.2Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KFF:(3-{(2S,4S)-4-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)-2-[(2-phosphonoethoxy)methyl]pyrrolidin-1-yl}-3-oxopropyl)phosphonic+acid'>KFF</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=8ts4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ts4 OCA], [https://pdbe.org/8ts4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ts4 RCSB], [https://www.ebi.ac.uk/pdbsum/8ts4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ts4 ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/HPRT_TRYBB HPRT_TRYBB] 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 (By similarity).
		+	<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~~:	+	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~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 8ts4" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Trypanosoma brucei]]
		+	[[Category: Guddat LW]]

OCA at 06:28, 10 April 2024

OCA — Wed, 10 Apr 2024 06:28:43 GMT

←Older revision		Revision as of 06:28, 10 April 2024
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8ts4 is ON HOLD	+	The entry 8ts4 is ON HOLD until Paper Publication

	Authors:		Authors:

OCA at 12:09, 13 March 2024

OCA — Wed, 13 Mar 2024 12:09:25 GMT

←Older revision		Revision as of 12:09, 13 March 2024
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8ts4 is ON HOLD ~~until sometime in the future~~	+	The entry 8ts4 is ON HOLD

	Authors:		Authors:

OCA at 04:48, 23 August 2023

OCA — Wed, 23 Aug 2023 04:48:34 GMT

←Older revision		Revision as of 04:48, 23 August 2023
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8ts4 is ON HOLD	+	The entry 8ts4 is ON HOLD until sometime in the future

	Authors:		Authors:

OCA: Protected "8ts4" [edit=sysop:move=sysop]

OCA — Wed, 16 Aug 2023 07:01:02 GMT

Protected "8ts4" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:01, 16 August 2023

OCA: New page: '''Unreleased structure''' The entry 8ts4 is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 16 Aug 2023 07:01:01 GMT

New page: '''Unreleased structure''' The entry 8ts4 is ON HOLD Authors: Description: Category: Unreleased Structures

New page