3arn - Revision history

OCA at 14:01, 13 March 2024

2024-03-13T14:01:38Z

← Older revision		Revision as of 14:01, 13 March 2024
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	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/DUT_HUMAN DUT_HUMAN] This enzyme is involved in nucleotide metabolism: it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA.<ref>PMID:8805593</ref>		[https://www.uniprot.org/uniprot/DUT_HUMAN DUT_HUMAN] This enzyme is involved in nucleotide metabolism: it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA.<ref>PMID:8805593</ref>
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	Inhibition of human deoxyuridine triphosphatase (dUTPase) has been identified as a promising approach to enhance the efficacy of 5-fluorouracil (5-FU)-based chemotherapy. This study describes the development of a novel class of dUTPase inhibitors based on the structure-activity relationship (SAR) studies of uracil derivatives. Starting from the weak inhibitor 7 (IC(50) = 100 muM), we developed compound 26, which is the most potent human dUTPase inhibitor (IC(50) = 0.021 muM) reported to date. Not only does compound 26 significantly enhance the growth inhibition activity of 5-fluoro-2'-deoxyuridine (FdUrd) against HeLa S3 cells in vitro (EC(50) = 0.075 muM) but also shows robust antitumor activity against MX-1 breast cancer xenograft model in mice when administered orally with a continuous infusion of 5-FU. This is the first in vivo evidence that human dUTPase inhibitors enhance the antitumor activity of TS inhibitors. On the basis of these findings, it was concluded that compound 26 is a promising candidate for clinical development.

	Discovery of a novel class of potent human deoxyuridine triphosphatase inhibitors remarkably enhancing the antitumor activity of thymidylate synthase inhibitors.,Miyahara S, Miyakoshi H, Yokogawa T, Chong KT, Taguchi J, Muto T, Endoh K, Yano W, Wakasa T, Ueno H, Takao Y, Fujioka A, Hashimoto A, Itou K, Yamamura K, Nomura M, Nagasawa H, Shuto S, Fukuoka M J Med Chem. 2012 Apr 12;55(7):2970-80. Epub 2012 Mar 26. PMID:22339362<ref>PMID:22339362</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 3arn" style="background-color:#fffaf0;"></div>~~

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

OCA at 15:53, 4 October 2023

2023-10-04T15:53:06Z

← Older revision		Revision as of 15:53, 4 October 2023
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	<StructureSection load='3arn' size='340' side='right'caption='[[3arn]], [[Resolution\|resolution]] 1.80Å' scene=''>		<StructureSection load='3arn' size='340' side='right'caption='[[3arn]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3arn]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ARN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ARN FirstGlance]. <br>		<table><tr><td colspan='2'>[[3arn]] 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=3ARN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ARN FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MSJ:N-{5-[(2,4-DIOXO-3,4-DIHYDROPYRIMIDIN-1(2H)-YL)METHOXY]-2-METHYLPENTAN-2-YL}BENZENESULFONAMIDE'>MSJ</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]] 1.8Å</td></tr>
	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3ara\|3ara]], [[2hqu\|2hqu]]</div></td></tr>~~		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MSJ:N-{5-[(2,4-DIOXO-3,4-DIHYDROPYRIMIDIN-1(2H)-YL)METHOXY]-2-METHYLPENTAN-2-YL}BENZENESULFONAMIDE'>MSJ</scene></td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/dUTP_diphosphatase dUTP diphosphatase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.1.23 3.6.1.23] </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=3arn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3arn OCA], [https://pdbe.org/3arn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3arn RCSB], [https://www.ebi.ac.uk/pdbsum/3arn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3arn 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=3arn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3arn OCA], [https://pdbe.org/3arn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3arn RCSB], [https://www.ebi.ac.uk/pdbsum/3arn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3arn ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/DUT_HUMAN DUT_HUMAN]] This enzyme is involved in nucleotide metabolism: it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA.<ref>PMID:8805593</ref>		[https://www.uniprot.org/uniprot/DUT_HUMAN DUT_HUMAN] This enzyme is involved in nucleotide metabolism: it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA.<ref>PMID:8805593</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	~~[[Category: DUTP diphosphatase]]~~		[[Category: Chong KT]]
	[[Category: Chong~~, K T~~]]		[[Category: Fukuoka M]]
	[[Category: Fukuoka, M]]		[[Category: Miyahara S]]
	[[Category: Miyahara, S]]		[[Category: Miyakoshi H]]
	[[Category: Miyakoshi, H]]
	~~[[Category: Hydrolase]]~~
	~~[[Category: Hydrolase-hydrolase inhibitor complex~~]]

OCA at 15:02, 29 December 2021

2021-12-29T15:02:08Z

← Older revision		Revision as of 15:02, 29 December 2021
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	<StructureSection load='3arn' size='340' side='right'caption='[[3arn]], [[Resolution\|resolution]] 1.80Å' scene=''>		<StructureSection load='3arn' size='340' side='right'caption='[[3arn]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3arn]] 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=3ARN OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3ARN FirstGlance]. <br>		<table><tr><td colspan='2'>[[3arn]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ARN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ARN FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MSJ:N-{5-[(2,4-DIOXO-3,4-DIHYDROPYRIMIDIN-1(2H)-YL)METHOXY]-2-METHYLPENTAN-2-YL}BENZENESULFONAMIDE'>MSJ</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MSJ:N-{5-[(2,4-DIOXO-3,4-DIHYDROPYRIMIDIN-1(2H)-YL)METHOXY]-2-METHYLPENTAN-2-YL}BENZENESULFONAMIDE'>MSJ</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3ara\|3ara]], [[2hqu\|2hqu]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3ara\|3ara]], [[2hqu\|2hqu]]</div></td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://en.wikipedia.org/wiki/dUTP_diphosphatase dUTP diphosphatase], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.1.23 3.6.1.23] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/dUTP_diphosphatase dUTP diphosphatase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.1.23 3.6.1.23] </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=3arn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3arn OCA], [~~http~~://pdbe.org/3arn PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3arn RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3arn PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3arn 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=3arn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3arn OCA], [https://pdbe.org/3arn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3arn RCSB], [https://www.ebi.ac.uk/pdbsum/3arn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3arn ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[~~http~~://www.uniprot.org/uniprot/DUT_HUMAN DUT_HUMAN]] This enzyme is involved in nucleotide metabolism: it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA.<ref>PMID:8805593</ref>		[[https://www.uniprot.org/uniprot/DUT_HUMAN DUT_HUMAN]] This enzyme is involved in nucleotide metabolism: it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA.<ref>PMID:8805593</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 07:30, 31 July 2019

2019-07-31T07:30:11Z

← Older revision		Revision as of 07:30, 31 July 2019
Line 1:		Line 1:

	==Human dUTPase in complex with novel uracil derivative==		==Human dUTPase in complex with novel uracil derivative==
	<StructureSection load='3arn' size='340' side='right' caption='[[3arn]], [[Resolution\|resolution]] 1.80Å' scene=''>		<StructureSection load='3arn' size='340' side='right'caption='[[3arn]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3arn]] 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=3ARN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ARN FirstGlance]. <br>		<table><tr><td colspan='2'>[[3arn]] 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=3ARN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ARN FirstGlance]. <br>
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	</div>		</div>
	<div class="pdbe-citations 3arn" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3arn" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[DUTPase 3D structures\|DUTPase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
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	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
			[[Category: Large Structures]]
	[[Category: DUTP diphosphatase]]		[[Category: DUTP diphosphatase]]
	[[Category: Chong, K T]]		[[Category: Chong, K T]]

OCA at 08:31, 12 October 2017

2017-10-12T08:31:37Z

← Older revision		Revision as of 08:31, 12 October 2017
Line 20:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 3arn" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3arn" style="background-color:#fffaf0;"></div>

	~~==See Also==~~
	*[[Deoxyuridine 5'-triphosphate nucleotidohydrolase\|Deoxyuridine 5'-triphosphate nucleotidohydrolase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 13:22, 5 August 2016

2016-08-05T13:22:21Z

← Older revision		Revision as of 13:22, 5 August 2016
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	==Human dUTPase in complex with novel uracil derivative==		==Human dUTPase in complex with novel uracil derivative==
	<StructureSection load='3arn' size='340' side='right' caption='[[3arn]], [[Resolution\|resolution]] 1.80Å' scene=''>		<StructureSection load='3arn' size='340' side='right' caption='[[3arn]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3arn]] 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=3ARN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ARN FirstGlance]. <br>		<table><tr><td colspan='2'>[[3arn]] 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=3ARN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ARN FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MSJ:N-{5-[(2,4-DIOXO-3,4-DIHYDROPYRIMIDIN-1(2H)-YL)METHOXY]-2-METHYLPENTAN-2-YL}BENZENESULFONAMIDE'>MSJ</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MSJ:N-{5-[(2,4-DIOXO-3,4-DIHYDROPYRIMIDIN-1(2H)-YL)METHOXY]-2-METHYLPENTAN-2-YL}BENZENESULFONAMIDE'>MSJ</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3ara\|3ara]], [[2hqu\|2hqu]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3ara\|3ara]], [[2hqu\|2hqu]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/dUTP_diphosphatase dUTP diphosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.1.23 3.6.1.23] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/dUTP_diphosphatase dUTP diphosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.1.23 3.6.1.23] </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=3arn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3arn OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3arn RCSB], [http://www.ebi.ac.uk/pdbsum/3arn 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=3arn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3arn OCA], [http://pdbe.org/3arn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3arn RCSB], [http://www.ebi.ac.uk/pdbsum/3arn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3arn ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
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	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 3arn" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 25:		Line 27:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Homo sapiens~~]]		[[Category: Human]]
	[[Category: DUTP diphosphatase]]		[[Category: DUTP diphosphatase]]
	[[Category: Chong, K T]]		[[Category: Chong, K T]]

OCA at 19:10, 25 December 2014

2014-12-25T19:10:16Z

← Older revision		Revision as of 19:10, 25 December 2014
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	<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=3arn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3arn OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3arn RCSB], [http://www.ebi.ac.uk/pdbsum/3arn 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=3arn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3arn OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3arn RCSB], [http://www.ebi.ac.uk/pdbsum/3arn PDBsum]</span></td></tr>
	</table>		</table>
			== Function ==
			[[http://www.uniprot.org/uniprot/DUT_HUMAN DUT_HUMAN]] This enzyme is involved in nucleotide metabolism: it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA.<ref>PMID:8805593</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 25:		Line 27:
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: DUTP diphosphatase]]		[[Category: DUTP diphosphatase]]
	[[Category: Chong, K T.]]		[[Category: Chong, K T]]
	[[Category: Fukuoka, M.]]		[[Category: Fukuoka, M]]
	[[Category: Miyahara, S.]]		[[Category: Miyahara, S]]
	[[Category: Miyakoshi, H.]]		[[Category: Miyakoshi, H]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]
	[[Category: Hydrolase-hydrolase inhibitor complex]]		[[Category: Hydrolase-hydrolase inhibitor complex]]

OCA at 09:28, 5 November 2014

2014-11-05T09:28:57Z

← Older revision		Revision as of 09:28, 5 November 2014
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	[[~~Image~~:~~3arn~~.~~png~~\|~~left~~\|~~200px~~]]		==Human dUTPase in complex with novel uracil derivative==
			<StructureSection load='3arn' size='340' side='right' caption='[[3arn]], [[Resolution\|resolution]] 1.80Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[3arn]] 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=3ARN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ARN FirstGlance]. <br>
			</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MSJ:N-{5-[(2,4-DIOXO-3,4-DIHYDROPYRIMIDIN-1(2H)-YL)METHOXY]-2-METHYLPENTAN-2-YL}BENZENESULFONAMIDE'>MSJ</scene></td></tr>
			<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3ara\|3ara]], [[2hqu\|2hqu]]</td></tr>
			<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/dUTP_diphosphatase dUTP diphosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.1.23 3.6.1.23] </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=3arn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3arn OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3arn RCSB], [http://www.ebi.ac.uk/pdbsum/3arn PDBsum]</span></td></tr>
			</table>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Inhibition of human deoxyuridine triphosphatase (dUTPase) has been identified as a promising approach to enhance the efficacy of 5-fluorouracil (5-FU)-based chemotherapy. This study describes the development of a novel class of dUTPase inhibitors based on the structure-activity relationship (SAR) studies of uracil derivatives. Starting from the weak inhibitor 7 (IC(50) = 100 muM), we developed compound 26, which is the most potent human dUTPase inhibitor (IC(50) = 0.021 muM) reported to date. Not only does compound 26 significantly enhance the growth inhibition activity of 5-fluoro-2'-deoxyuridine (FdUrd) against HeLa S3 cells in vitro (EC(50) = 0.075 muM) but also shows robust antitumor activity against MX-1 breast cancer xenograft model in mice when administered orally with a continuous infusion of 5-FU. This is the first in vivo evidence that human dUTPase inhibitors enhance the antitumor activity of TS inhibitors. On the basis of these findings, it was concluded that compound 26 is a promising candidate for clinical development.

	~~{{STRUCTURE_3arn\| PDB=3arn \| SCENE= }}~~		Discovery of a novel class of potent human deoxyuridine triphosphatase inhibitors remarkably enhancing the antitumor activity of thymidylate synthase inhibitors.,Miyahara S, Miyakoshi H, Yokogawa T, Chong KT, Taguchi J, Muto T, Endoh K, Yano W, Wakasa T, Ueno H, Takao Y, Fujioka A, Hashimoto A, Itou K, Yamamura K, Nomura M, Nagasawa H, Shuto S, Fukuoka M J Med Chem. 2012 Apr 12;55(7):2970-80. Epub 2012 Mar 26. PMID:22339362<ref>PMID:22339362</ref>

	~~===Human dUTPase in complex with novel uracil derivative===~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
	~~{{ABSTRACT_PUBMED_22339362}}~~

	~~==About this Structure==~~
	~~[[3arn]] 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=3ARN OCA].~~

	==See Also==		==See Also==
	*[[Deoxyuridine 5'-triphosphate nucleotidohydrolase\|Deoxyuridine 5'-triphosphate nucleotidohydrolase]]		*[[Deoxyuridine 5'-triphosphate nucleotidohydrolase\|Deoxyuridine 5'-triphosphate nucleotidohydrolase]]
			== References ==
	==~~Reference~~==		<references/>
	<~~ref group="xtra">PMID:022339362<~~/~~ref~~><~~references group="xtra"~~/>		__TOC__
			</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: DUTP diphosphatase]]		[[Category: DUTP diphosphatase]]

OCA at 20:23, 20 October 2012

2012-10-20T20:23:24Z

← Older revision		Revision as of 20:23, 20 October 2012
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	==About this Structure==		==About this Structure==
	[[3arn]] is a 3 chain structure ~~of [[Deoxyuridine 5'-triphosphate nucleotidohydrolase]]~~ 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=3ARN OCA].		[[3arn]] 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=3ARN OCA].

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

OCA at 10:19, 27 July 2012

2012-07-27T10:19:09Z

← Older revision		Revision as of 10:19, 27 July 2012
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	[[Image:3arn.png\|left\|200px]]		[[Image:3arn.png\|left\|200px]]

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	===Human dUTPase in complex with novel uracil derivative===		===Human dUTPase in complex with novel uracil derivative===


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