4raq - Revision history

OCA at 12:51, 1 March 2024

2024-03-01T12:51:18Z

← Older revision		Revision as of 12:51, 1 March 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4raq]] 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=4RAQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RAQ FirstGlance]. <br>		<table><tr><td colspan='2'>[[4raq]] 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=4RAQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RAQ FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3L8:[(2-{[2-(6-OXO-1,6-DIHYDRO-9H-PURIN-9-YL)ETHYL](2-PHOSPHONOETHYL)AMINO}ETHOXY)METHYL]PHOSPHONIC+ACID'>3L8</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]] 2.53Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3L8:[(2-{[2-(6-OXO-1,6-DIHYDRO-9H-PURIN-9-YL)ETHYL](2-PHOSPHONOETHYL)AMINO}ETHOXY)METHYL]PHOSPHONIC+ACID'>3L8</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=4raq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4raq OCA], [https://pdbe.org/4raq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4raq RCSB], [https://www.ebi.ac.uk/pdbsum/4raq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4raq 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=4raq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4raq OCA], [https://pdbe.org/4raq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4raq RCSB], [https://www.ebi.ac.uk/pdbsum/4raq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4raq ProSAT]</span></td></tr>
	</table>		</table>
Line 11:		Line 12:
	== Function ==		== 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.		[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 ==~~
	Hypoxanthine-guanine-[xanthine] phosphoribosyltransferase (HG[X]PRT) is considered an important target for antimalarial chemotherapy as it is the only pathway for the synthesis of the purine nucleoside monophosphates required for DNA/RNA production. Thus, inhibition of this enzyme should result in cessation of replication. The aza-acyclic nucleoside phosphonates (aza-ANPs) are good inhibitors of Plasmodium falciparum HGXPRT (PfHGXPRT), with Ki values as low as 0.08 and 0.01 muM for Plasmodium vivax HGPRT (PvHGPRT). Prodrugs of these aza-ANPs exhibit antimalarial activity against Pf lines with IC50 values (0.8-6.0 muM) and have low cytotoxicity against human cells. Crystal structures of six of these compounds in complex with human HGPRT have been determined. These suggest that the different affinities of these aza-ANPs could be due to the flexibility of the loops surrounding the active site as well as the flexibility of the inhibitors, allowing them to adapt to fit into three binding pockets of the enzyme(s).

	Aza-acyclic Nucleoside Phosphonates Containing a Second Phosphonate Group As Inhibitors of the Human, Plasmodium falciparum and vivax 6-Oxopurine Phosphoribosyltransferases and Their Prodrugs As Antimalarial Agents.,Keough DT, Hockova D, Janeba Z, Wang T, Naesens L, Edstein MD, Chavchich M, Guddat LW J Med Chem. 2014 Dec 24. PMID:25494538<ref>PMID:25494538</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 4raq" style="background-color:#fffaf0;"></div>~~

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

OCA at 06:47, 2 March 2023

2023-03-02T06:47:52Z

← Older revision		Revision as of 06:47, 2 March 2023
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	<StructureSection load='4raq' size='340' side='right'caption='[[4raq]], [[Resolution\|resolution]] 2.53Å' scene=''>		<StructureSection load='4raq' size='340' side='right'caption='[[4raq]], [[Resolution\|resolution]] 2.53Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4raq]] is a 4 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=4RAQ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4RAQ FirstGlance]. <br>		<table><tr><td colspan='2'>[[4raq]] 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=4RAQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RAQ FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3L8:[(2-{[2-(6-OXO-1,6-DIHYDRO-9H-PURIN-9-YL)ETHYL](2-PHOSPHONOETHYL)AMINO}ETHOXY)METHYL]PHOSPHONIC+ACID'>3L8</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=3L8:[(2-{[2-(6-OXO-1,6-DIHYDRO-9H-PURIN-9-YL)ETHYL](2-PHOSPHONOETHYL)AMINO}ETHOXY)METHYL]PHOSPHONIC+ACID'>3L8</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4rab\|4rab]], [[4rac\|4rac]], [[4rad\|4rad]], [[4ran\|4ran]], [[4rao\|4rao]]</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=4raq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4raq OCA], [https://pdbe.org/4raq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4raq RCSB], [https://www.ebi.ac.uk/pdbsum/4raq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4raq ProSAT]</span></td></tr>
	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HPRT1, HPRT ([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/Hypoxanthine_phosphoribosyltransferase Hypoxanthine phosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.8 2.4.2.8] </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=4raq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4raq OCA], [~~http~~://pdbe.org/4raq PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4raq RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4raq PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4raq ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[~~[http~~://www.uniprot.org/uniprot/HPRT_HUMAN HPRT_HUMAN]] Defects in HPRT1 are the cause of Lesch-Nyhan syndrome (LNS) [MIM:[~~http~~://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:[~~http~~://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> [:]		[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 ==		== Function ==
	[~~[http~~://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.		[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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	==See Also==		==See Also==
	*[[Phosphoribosyltransferase\|Phosphoribosyltransferase]]		*[[Phosphoribosyltransferase 3D structures\|Phosphoribosyltransferase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human]]~~		[[Category: Homo sapiens]]
	~~[[Category: Hypoxanthine phosphoribosyltransferase~~]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Chavchich, M]]		[[Category: Chavchich M]]
	[[Category: Edstein~~, M D~~]]		[[Category: Edstein MD]]
	[[Category: Guddat~~, L W~~]]		[[Category: Guddat LW]]
	[[Category: Hockova, D]]		[[Category: Hockova D]]
	[[Category: Janeba, Z]]		[[Category: Janeba Z]]
	[[Category: Keough~~, D T~~]]		[[Category: Keough DT]]
	[[Category: Naesens, L]]		[[Category: Naesens L]]
	[[Category: Wang, T H]]		[[Category: Wang T-H]]
	~~[[Category: 6-oxopurine phosphoribosyltransferase]]~~
	~~[[Category: Acyclic nucleoside monophosphonate]]~~
	~~[[Category: Cytoplasmic]]~~
	~~[[Category: Hypoxanthine-guanine phosphoribosyltransferase]]~~
	~~[[Category: Malaria]]~~
	~~[[Category: Transferase-transferase inhibitor complex~~]]

OCA at 09:43, 1 May 2019

2019-05-01T09:43:45Z

← Older revision		Revision as of 09:43, 1 May 2019
Line 1:		Line 1:

	==Aza-acyclic nucleoside phosphonates containing a second phosphonate group as inhibitors of the human, Plasmodium falciparum and vivax 6-oxopurine phosphoribosyltransferases and their pro-drugs as antimalarial agents==		==Aza-acyclic nucleoside phosphonates containing a second phosphonate group as inhibitors of the human, Plasmodium falciparum and vivax 6-oxopurine phosphoribosyltransferases and their pro-drugs as antimalarial agents==
	<StructureSection load='4raq' size='340' side='right' caption='[[4raq]], [[Resolution\|resolution]] 2.53Å' scene=''>		<StructureSection load='4raq' size='340' side='right'caption='[[4raq]], [[Resolution\|resolution]] 2.53Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4raq]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RAQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RAQ FirstGlance]. <br>		<table><tr><td colspan='2'>[[4raq]] is a 4 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=4RAQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RAQ FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3L8:[(2-{[2-(6-OXO-1,6-DIHYDRO-9H-PURIN-9-YL)ETHYL](2-PHOSPHONOETHYL)AMINO}ETHOXY)METHYL]PHOSPHONIC+ACID'>3L8</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=3L8:[(2-{[2-(6-OXO-1,6-DIHYDRO-9H-PURIN-9-YL)ETHYL](2-PHOSPHONOETHYL)AMINO}ETHOXY)METHYL]PHOSPHONIC+ACID'>3L8</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4rab\|4rab]], [[4rac\|4rac]], [[4rad\|4rad]], [[4ran\|4ran]], [[4rao\|4rao]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4rab\|4rab]], [[4rac\|4rac]], [[4rad\|4rad]], [[4ran\|4ran]], [[4rao\|4rao]]</td></tr>
			<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HPRT1, HPRT ([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/Hypoxanthine_phosphoribosyltransferase Hypoxanthine phosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.8 2.4.2.8] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Hypoxanthine_phosphoribosyltransferase Hypoxanthine phosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.8 2.4.2.8] </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=4raq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4raq OCA], [http://pdbe.org/4raq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4raq RCSB], [http://www.ebi.ac.uk/pdbsum/4raq 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=4raq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4raq OCA], [http://pdbe.org/4raq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4raq RCSB], [http://www.ebi.ac.uk/pdbsum/4raq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4raq ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Human]]
	[[Category: Hypoxanthine phosphoribosyltransferase]]		[[Category: Hypoxanthine phosphoribosyltransferase]]
			[[Category: Large Structures]]
	[[Category: Chavchich, M]]		[[Category: Chavchich, M]]
	[[Category: Edstein, M D]]		[[Category: Edstein, M D]]

OCA at 06:17, 23 December 2015

2015-12-23T06:17:59Z

← Older revision		Revision as of 06:17, 23 December 2015
Line 6:		Line 6:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4rab\|4rab]], [[4rac\|4rac]], [[4rad\|4rad]], [[4ran\|4ran]], [[4rao\|4rao]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4rab\|4rab]], [[4rac\|4rac]], [[4rad\|4rad]], [[4ran\|4ran]], [[4rao\|4rao]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Hypoxanthine_phosphoribosyltransferase Hypoxanthine phosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.8 2.4.2.8] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Hypoxanthine_phosphoribosyltransferase Hypoxanthine phosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.8 2.4.2.8] </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=4raq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4raq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4raq RCSB], [http://www.ebi.ac.uk/pdbsum/4raq 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=4raq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4raq OCA], [http://pdbe.org/4raq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4raq RCSB], [http://www.ebi.ac.uk/pdbsum/4raq PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 20:		Line 20:
	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 4raq" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Phosphoribosyltransferase\|Phosphoribosyltransferase]]
	== References ==		== References ==
	<references/>		<references/>
Line 28:		Line 32:
	[[Category: Edstein, M D]]		[[Category: Edstein, M D]]
	[[Category: Guddat, L W]]		[[Category: Guddat, L W]]
	[[Category: ~~Hockov~~, D]]		[[Category: Hockova, D]]
	[[Category: Janeba, Z]]		[[Category: Janeba, Z]]
	[[Category: Keough, D T]]		[[Category: Keough, D T]]

OCA at 16:16, 7 January 2015

2015-01-07T16:16:19Z

← Older revision		Revision as of 16:16, 7 January 2015
Line 1:		Line 1:
	'''~~Unreleased~~ structure'''		==Aza-acyclic nucleoside phosphonates containing a second phosphonate group as inhibitors of the human, Plasmodium falciparum and vivax 6-oxopurine phosphoribosyltransferases and their pro-drugs as antimalarial agents==
			<StructureSection load='4raq' size='340' side='right' caption='[[4raq]], [[Resolution\|resolution]] 2.53Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[4raq]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RAQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RAQ FirstGlance]. <br>
			</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3L8:[(2-{[2-(6-OXO-1,6-DIHYDRO-9H-PURIN-9-YL)ETHYL](2-PHOSPHONOETHYL)AMINO}ETHOXY)METHYL]PHOSPHONIC+ACID'>3L8</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
			<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4rab\|4rab]], [[4rac\|4rac]], [[4rad\|4rad]], [[4ran\|4ran]], [[4rao\|4rao]]</td></tr>
			<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Hypoxanthine_phosphoribosyltransferase Hypoxanthine phosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.8 2.4.2.8] </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=4raq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4raq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4raq RCSB], [http://www.ebi.ac.uk/pdbsum/4raq PDBsum]</span></td></tr>
			</table>
			== Disease ==
			[[http://www.uniprot.org/uniprot/HPRT_HUMAN HPRT_HUMAN]] Defects in HPRT1 are the cause of Lesch-Nyhan syndrome (LNS) [MIM:[http://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:[http://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 ==
			[[http://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 ==
			Hypoxanthine-guanine-[xanthine] phosphoribosyltransferase (HG[X]PRT) is considered an important target for antimalarial chemotherapy as it is the only pathway for the synthesis of the purine nucleoside monophosphates required for DNA/RNA production. Thus, inhibition of this enzyme should result in cessation of replication. The aza-acyclic nucleoside phosphonates (aza-ANPs) are good inhibitors of Plasmodium falciparum HGXPRT (PfHGXPRT), with Ki values as low as 0.08 and 0.01 muM for Plasmodium vivax HGPRT (PvHGPRT). Prodrugs of these aza-ANPs exhibit antimalarial activity against Pf lines with IC50 values (0.8-6.0 muM) and have low cytotoxicity against human cells. Crystal structures of six of these compounds in complex with human HGPRT have been determined. These suggest that the different affinities of these aza-ANPs could be due to the flexibility of the loops surrounding the active site as well as the flexibility of the inhibitors, allowing them to adapt to fit into three binding pockets of the enzyme(s).

	~~The entry 4raq is ON HOLD~~		Aza-acyclic Nucleoside Phosphonates Containing a Second Phosphonate Group As Inhibitors of the Human, Plasmodium falciparum and vivax 6-Oxopurine Phosphoribosyltransferases and Their Prodrugs As Antimalarial Agents.,Keough DT, Hockova D, Janeba Z, Wang T, Naesens L, Edstein MD, Chavchich M, Guddat LW J Med Chem. 2014 Dec 24. PMID:25494538<ref>PMID:25494538</ref>

	~~Authors: Keough~~, D.T.~~, Hockov, D., Janeba, Z., Wang, T.-H., Naesens, L., Edstein, M.D., Chavchich, M., Guddat, L.W~~.		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
	~~Description~~: ~~Aza-acyclic nucleoside phosphonates containing a second phosphonate group as inhibitors of the human~~, ~~Plasmodium falciparum and vivax 6-oxopurine phosphoribosyltransferases and their pro-drugs as antimalarial agents~~		== References ==
	[[Category: ~~Unreleased Structures~~]]		<references/>
	[[Category: ~~Naesens~~, L]]		__TOC__
			</StructureSection>
			[[Category: Hypoxanthine phosphoribosyltransferase]]
			[[Category: Chavchich, M]]
			[[Category: Edstein, M D]]
			[[Category: Guddat, L W]]
	[[Category: Hockov, D]]		[[Category: Hockov, D]]
	~~[[Category: Edstein, M.D]]~~
	~~[[Category: Keough, D.T]]~~
	[[Category: Janeba, Z]]		[[Category: Janeba, Z]]
	[[Category: ~~Chavchich~~, M]]		[[Category: Keough, D T]]
	[[Category: ~~Guddat~~, L.W]]		[[Category: Naesens, L]]
	[[Category: Wang, T.-H]]		[[Category: Wang, T H]]
			[[Category: 6-oxopurine phosphoribosyltransferase]]
			[[Category: Acyclic nucleoside monophosphonate]]
			[[Category: Cytoplasmic]]
			[[Category: Hypoxanthine-guanine phosphoribosyltransferase]]
			[[Category: Malaria]]
			[[Category: Transferase-transferase inhibitor complex]]

OCA at 16:41, 24 December 2014

2014-12-24T16:41:40Z

← Older revision		Revision as of 16:41, 24 December 2014
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	Description: Aza-acyclic nucleoside phosphonates containing a second phosphonate group as inhibitors of the human, Plasmodium falciparum and vivax 6-oxopurine phosphoribosyltransferases and their pro-drugs as antimalarial agents		Description: Aza-acyclic nucleoside phosphonates containing a second phosphonate group as inhibitors of the human, Plasmodium falciparum and vivax 6-oxopurine phosphoribosyltransferases and their pro-drugs as antimalarial agents
			[[Category: Unreleased Structures]]
			[[Category: Naesens, L]]
			[[Category: Hockov, D]]
			[[Category: Edstein, M.D]]
			[[Category: Keough, D.T]]
			[[Category: Janeba, Z]]
			[[Category: Chavchich, M]]
			[[Category: Guddat, L.W]]
			[[Category: Wang, T.-H]]

OCA: Protected "4raq" [edit=sysop:move=sysop]

2014-09-24T08:29:12Z

Protected "4raq" [edit=sysop:move=sysop]

← Older revision	Revision as of 08:29, 24 September 2014
(No difference)

OCA: New page: '''Unreleased structure''' The entry 4raq is ON HOLD Authors: Keough, D.T., Hockov, D., Janeba, Z., Wang, T.-H., Naesens, L., Edstein, M.D., Chavchich, M., Guddat, L.W. Description: Az...

2014-09-24T08:29:10Z

New page: '''Unreleased structure''' The entry 4raq is ON HOLD Authors: Keough, D.T., Hockov, D., Janeba, Z., Wang, T.-H., Naesens, L., Edstein, M.D., Chavchich, M., Guddat, L.W. Description: Az...

New page

'''Unreleased structure'''

The entry 4raq is ON HOLD

Authors: Keough, D.T., Hockov, D., Janeba, Z., Wang, T.-H., Naesens, L., Edstein, M.D., Chavchich, M., Guddat, L.W.

Description: Aza-acyclic nucleoside phosphonates containing a second phosphonate group as inhibitors of the human, Plasmodium falciparum and vivax 6-oxopurine phosphoribosyltransferases and their pro-drugs as antimalarial agents