1ju6 - Revision history

OCA at 06:04, 3 April 2024

OCA — Wed, 03 Apr 2024 06:04:40 GMT

←Older revision		Revision as of 06:04, 3 April 2024
Line 3:		Line 3:
	<StructureSection load='1ju6' size='340' side='right'caption='[[1ju6]], [[Resolution\|resolution]] 2.89Å' scene=''>		<StructureSection load='1ju6' size='340' side='right'caption='[[1ju6]], [[Resolution\|resolution]] 2.89Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1ju6]] is a 4 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=1JU6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1JU6 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1ju6]] 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=1JU6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1JU6 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LYA:2-{4-[2-(2-AMINO-4-OXO-4,7-DIHYDRO-3H-PYRROLO[2,3-D]PYRIMIDIN-5-YL)-ETHYL]-BENZOYLAMINO}-PENTANEDIOIC+ACID'>LYA</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=UMP:2-DEOXYURIDINE+5-MONOPHOSPHATE'>UMP</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]] 2.89Å</td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1jtq\|1jtq]], [[1jtu\|1jtu]], [[1juj\|1juj]], [[1jut\|1jut]]</div></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LYA:2-{4-[2-(2-AMINO-4-OXO-4,7-DIHYDRO-3H-PYRROLO[2,3-D]PYRIMIDIN-5-YL)-ETHYL]-BENZOYLAMINO}-PENTANEDIOIC+ACID'>LYA</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=UMP:2-DEOXYURIDINE+5-MONOPHOSPHATE'>UMP</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Thymidylate_synthase Thymidylate synthase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.45 2.1.1.45] </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=1ju6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ju6 OCA], [https://pdbe.org/1ju6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ju6 RCSB], [https://www.ebi.ac.uk/pdbsum/1ju6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ju6 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=1ju6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ju6 OCA], [https://pdbe.org/1ju6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ju6 RCSB], [https://www.ebi.ac.uk/pdbsum/1ju6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ju6 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/TYSY_HUMAN TYSY_HUMAN]] Contributes to the de novo mitochondrial thymidylate biosynthesis pathway.<ref>PMID:21876188</ref>	+	[https://www.uniprot.org/uniprot/TYSY_HUMAN TYSY_HUMAN] Contributes to the de novo mitochondrial thymidylate biosynthesis pathway.<ref>PMID:21876188</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 21:		Line 20:
	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1ju6 ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1ju6 ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Crystal structures of four pyrrolo(2,3-d)pyrimidine-based antifolate compounds, developed as inhibitors of thymidylate synthase (TS) in a strategy to circumvent drug-resistance, have been determined in complexes with their in vivo target, human thymidylate synthase, and with the structurally best-characterized Escherichia coli enzyme, to resolutions of 2.2-3.0 A. The 2.9 A crystal structure of a complex of human TS with one of the inhibitors, the multi-targeted antifolate LY231514, demonstrates that this compound induces a "closed" enzyme conformation and leads to formation of a covalent bond between enzyme and substrate. This structure is one of the first liganded human TS structures, and its solution was aided by mutation to facilitate crystallization. Structures of three other pyrrolo(2,3-d)pyrimidine-based antifolates in complex with Escherichia coli TS confirm the orientation of this class of inhibitors in the active site. Specific interactions between the polyglutamyl moiety and a positively charged groove on the enzyme surface explain the marked increase in affinity of the pyrrolo(2,3-d)pyrimidine inhibitors once they are polyglutamylated, as mediated in vivo by the cellular enzyme folyl polyglutamate synthetase.
-
-	Multi-targeted antifolates aimed at avoiding drug resistance form covalent closed inhibitory complexes with human and Escherichia coli thymidylate synthases.,Sayre PH, Finer-Moore JS, Fritz TA, Biermann D, Gates SB, MacKellar WC, Patel VF, Stroud RM J Mol Biol. 2001 Nov 2;313(4):813-29. PMID:11697906<ref>PMID:11697906</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 1ju6" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 37:		Line 27:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Thymidylate synthase]]~~	+	[[Category: Biermann D]]
-	[[Category: Biermann, D]]	+	[[Category: Finer-Moore JS]]
-	[[Category: Finer-Moore~~, J S~~]]	+	[[Category: Fritz TA]]
-	[[Category: Fritz~~, T A~~]]	+	[[Category: Gates SB]]
-	[[Category: Gates~~, S B~~]]	+	[[Category: MacKellar WC]]
-	[[Category: MacKellar~~, W C~~]]	+	[[Category: Patel VF]]
-	[[Category: Patel~~, V F~~]]	+	[[Category: Sayre PH]]
-	[[Category: Sayre~~, P H~~]]	+	[[Category: Stroud RM]]
-	[[Category: Stroud~~, R M]]~~	+
-	~~[[Category: Antifolate]]~~	+
-	~~[[Category: Cancer]]~~	+
-	~~[[Category: Drug resistance]]~~	+
-	~~[[Category: Dtmp synthesis]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 06:45, 11 August 2021

OCA — Wed, 11 Aug 2021 06:45:41 GMT

←Older revision		Revision as of 06:45, 11 August 2021
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	<StructureSection load='1ju6' size='340' side='right'caption='[[1ju6]], [[Resolution\|resolution]] 2.89Å' scene=''>		<StructureSection load='1ju6' size='340' side='right'caption='[[1ju6]], [[Resolution\|resolution]] 2.89Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1ju6]] 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=1JU6 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=1JU6 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1ju6]] is a 4 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=1JU6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1JU6 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LYA:2-{4-[2-(2-AMINO-4-OXO-4,7-DIHYDRO-3H-PYRROLO[2,3-D]PYRIMIDIN-5-YL)-ETHYL]-BENZOYLAMINO}-PENTANEDIOIC+ACID'>LYA</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=UMP:2-DEOXYURIDINE+5-MONOPHOSPHATE'>UMP</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LYA:2-{4-[2-(2-AMINO-4-OXO-4,7-DIHYDRO-3H-PYRROLO[2,3-D]PYRIMIDIN-5-YL)-ETHYL]-BENZOYLAMINO}-PENTANEDIOIC+ACID'>LYA</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=UMP:2-DEOXYURIDINE+5-MONOPHOSPHATE'>UMP</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1jtq\|1jtq]], [[1jtu\|1jtu]], [[1juj\|1juj]], [[1jut\|1jut]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1jtq\|1jtq]], [[1jtu\|1jtu]], [[1juj\|1juj]], [[1jut\|1jut]]</div></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://en.wikipedia.org/wiki/Thymidylate_synthase Thymidylate synthase], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.45 2.1.1.45] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Thymidylate_synthase Thymidylate synthase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.45 2.1.1.45] </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=1ju6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ju6 OCA], [~~http~~://pdbe.org/1ju6 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=1ju6 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/1ju6 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=1ju6 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=1ju6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ju6 OCA], [https://pdbe.org/1ju6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ju6 RCSB], [https://www.ebi.ac.uk/pdbsum/1ju6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ju6 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/TYSY_HUMAN TYSY_HUMAN]] Contributes to the de novo mitochondrial thymidylate biosynthesis pathway.<ref>PMID:21876188</ref>	+	[[https://www.uniprot.org/uniprot/TYSY_HUMAN TYSY_HUMAN]] Contributes to the de novo mitochondrial thymidylate biosynthesis pathway.<ref>PMID:21876188</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 32:		Line 32:

	==See Also==		==See Also==
-	*[[Thymidylate synthase\|Thymidylate synthase]]	+	*[[Thymidylate synthase 3D structures\|Thymidylate synthase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 09:36, 6 November 2019

OCA — Wed, 06 Nov 2019 09:36:58 GMT

←Older revision		Revision as of 09:36, 6 November 2019
Line 1:		Line 1:

	==Human Thymidylate Synthase Complex with dUMP and LY231514, A Pyrrolo(2,3-d)pyrimidine-based Antifolate==		==Human Thymidylate Synthase Complex with dUMP and LY231514, A Pyrrolo(2,3-d)pyrimidine-based Antifolate==
-	<StructureSection load='1ju6' size='340' side='right' caption='[[1ju6]], [[Resolution\|resolution]] 2.89Å' scene=''>	+	<StructureSection load='1ju6' size='340' side='right'caption='[[1ju6]], [[Resolution\|resolution]] 2.89Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1ju6]] 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=1JU6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1JU6 FirstGlance]. <br>		<table><tr><td colspan='2'>[[1ju6]] 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=1JU6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1JU6 FirstGlance]. <br>
Line 30:		Line 30:
	</div>		</div>
	<div class="pdbe-citations 1ju6" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1ju6" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Thymidylate synthase\|Thymidylate synthase]]
	== References ==		== References ==
	<references/>		<references/>
Line 35:		Line 38:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Thymidylate synthase]]		[[Category: Thymidylate synthase]]
	[[Category: Biermann, D]]		[[Category: Biermann, D]]

OCA at 09:11, 17 January 2018

OCA — Wed, 17 Jan 2018 09:11:59 GMT

←Older revision		Revision as of 09:11, 17 January 2018
Line 1:		Line 1:
		+
	==Human Thymidylate Synthase Complex with dUMP and LY231514, A Pyrrolo(2,3-d)pyrimidine-based Antifolate==		==Human Thymidylate Synthase Complex with dUMP and LY231514, A Pyrrolo(2,3-d)pyrimidine-based Antifolate==
	<StructureSection load='1ju6' size='340' side='right' caption='[[1ju6]], [[Resolution\|resolution]] 2.89Å' scene=''>		<StructureSection load='1ju6' size='340' side='right' caption='[[1ju6]], [[Resolution\|resolution]] 2.89Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1jtq\|1jtq]], [[1jtu\|1jtu]], [[1juj\|1juj]], [[1jut\|1jut]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1jtq\|1jtq]], [[1jtu\|1jtu]], [[1juj\|1juj]], [[1jut\|1jut]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thymidylate_synthase Thymidylate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.45 2.1.1.45] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thymidylate_synthase Thymidylate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.45 2.1.1.45] </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=1ju6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ju6 OCA], [http://pdbe.org/1ju6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ju6 RCSB], [http://www.ebi.ac.uk/pdbsum/1ju6 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=1ju6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ju6 OCA], [http://pdbe.org/1ju6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ju6 RCSB], [http://www.ebi.ac.uk/pdbsum/1ju6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1ju6 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 14:		Line 15:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ju/1ju6_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ju/1ju6_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
Line 29:		Line 30:
	</div>		</div>
	<div class="pdbe-citations 1ju6" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1ju6" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Thymidylate synthase\|Thymidylate synthase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 05:02, 9 February 2016

OCA — Tue, 09 Feb 2016 05:02:49 GMT

←Older revision		Revision as of 05:02, 9 February 2016
Line 18:		Line 18:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
-	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].	+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1ju6 ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 18:53, 10 September 2015

OCA — Thu, 10 Sep 2015 18:53:24 GMT

←Older revision		Revision as of 18:53, 10 September 2015
Line 2:		Line 2:
	<StructureSection load='1ju6' size='340' side='right' caption='[[1ju6]], [[Resolution\|resolution]] 2.89Å' scene=''>		<StructureSection load='1ju6' size='340' side='right' caption='[[1ju6]], [[Resolution\|resolution]] 2.89Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1ju6]] is a 4 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=1JU6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1JU6 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1ju6]] 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=1JU6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1JU6 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LYA:2-{4-[2-(2-AMINO-4-OXO-4,7-DIHYDRO-3H-PYRROLO[2,3-D]PYRIMIDIN-5-YL)-ETHYL]-BENZOYLAMINO}-PENTANEDIOIC+ACID'>LYA</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=UMP:2-DEOXYURIDINE+5-MONOPHOSPHATE'>UMP</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LYA:2-{4-[2-(2-AMINO-4-OXO-4,7-DIHYDRO-3H-PYRROLO[2,3-D]PYRIMIDIN-5-YL)-ETHYL]-BENZOYLAMINO}-PENTANEDIOIC+ACID'>LYA</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=UMP:2-DEOXYURIDINE+5-MONOPHOSPHATE'>UMP</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1jtq\|1jtq]], [[1jtu\|1jtu]], [[1juj\|1juj]], [[1jut\|1jut]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1jtq\|1jtq]], [[1jtu\|1jtu]], [[1juj\|1juj]], [[1jut\|1jut]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thymidylate_synthase Thymidylate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.45 2.1.1.45] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thymidylate_synthase Thymidylate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.45 2.1.1.45] </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=1ju6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ju6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1ju6 RCSB], [http://www.ebi.ac.uk/pdbsum/1ju6 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=1ju6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ju6 OCA], [http://pdbe.org/1ju6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ju6 RCSB], [http://www.ebi.ac.uk/pdbsum/1ju6 PDBsum]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 28:		Line 28:
	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 1ju6" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 35:		Line 36:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Thymidylate synthase]]		[[Category: Thymidylate synthase]]
	[[Category: Biermann, D]]		[[Category: Biermann, D]]

OCA at 04:36, 25 December 2014

OCA — Thu, 25 Dec 2014 04:36:46 GMT

←Older revision		Revision as of 04:36, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1ju6]] is a 4 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=1JU6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1JU6 FirstGlance]. <br>		<table><tr><td colspan='2'>[[1ju6]] is a 4 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=1JU6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1JU6 FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LYA:2-{4-[2-(2-AMINO-4-OXO-4,7-DIHYDRO-3H-PYRROLO[2,3-D]PYRIMIDIN-5-YL)-ETHYL]-BENZOYLAMINO}-PENTANEDIOIC+ACID'>LYA</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=UMP:2-DEOXYURIDINE+5-MONOPHOSPHATE'>UMP</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LYA:2-{4-[2-(2-AMINO-4-OXO-4,7-DIHYDRO-3H-PYRROLO[2,3-D]PYRIMIDIN-5-YL)-ETHYL]-BENZOYLAMINO}-PENTANEDIOIC+ACID'>LYA</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=UMP:2-DEOXYURIDINE+5-MONOPHOSPHATE'>UMP</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1jtq\|1jtq]], [[1jtu\|1jtu]], [[1juj\|1juj]], [[1jut\|1jut]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1jtq\|1jtq]], [[1jtu\|1jtu]], [[1juj\|1juj]], [[1jut\|1jut]]</td></tr>
-	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thymidylate_synthase Thymidylate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.45 2.1.1.45] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thymidylate_synthase Thymidylate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.45 2.1.1.45] </span></td></tr>
-	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ju6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ju6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1ju6 RCSB], [http://www.ebi.ac.uk/pdbsum/1ju6 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=1ju6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ju6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1ju6 RCSB], [http://www.ebi.ac.uk/pdbsum/1ju6 PDBsum]</span></td></tr>
-	<table>	+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/TYSY_HUMAN TYSY_HUMAN]] Contributes to the de novo mitochondrial thymidylate biosynthesis pathway.<ref>PMID:21876188</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 35:		Line 37:
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Thymidylate synthase]]		[[Category: Thymidylate synthase]]
-	[[Category: Biermann, D.]]	+	[[Category: Biermann, D]]
-	[[Category: Finer-Moore, J S.]]	+	[[Category: Finer-Moore, J S]]
-	[[Category: Fritz, T A.]]	+	[[Category: Fritz, T A]]
-	[[Category: Gates, S B.]]	+	[[Category: Gates, S B]]
-	[[Category: MacKellar, W C.]]	+	[[Category: MacKellar, W C]]
-	[[Category: Patel, V F.]]	+	[[Category: Patel, V F]]
-	[[Category: Sayre, P H.]]	+	[[Category: Sayre, P H]]
-	[[Category: Stroud, R M.]]	+	[[Category: Stroud, R M]]
	[[Category: Antifolate]]		[[Category: Antifolate]]
	[[Category: Cancer]]		[[Category: Cancer]]

OCA at 11:24, 28 September 2014

OCA — Sun, 28 Sep 2014 11:24:15 GMT

←Older revision		Revision as of 11:24, 28 September 2014
Line 1:		Line 1:
-	[[~~Image:~~1ju6.~~png~~\|~~left~~\|200px]]	+	==Human Thymidylate Synthase Complex with dUMP and LY231514, A Pyrrolo(2,3-d)pyrimidine-based Antifolate==
		+	<StructureSection load='1ju6' size='340' side='right' caption='[[1ju6]], [[Resolution\|resolution]] 2.89Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[1ju6]] is a 4 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=1JU6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1JU6 FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LYA:2-{4-[2-(2-AMINO-4-OXO-4,7-DIHYDRO-3H-PYRROLO[2,3-D]PYRIMIDIN-5-YL)-ETHYL]-BENZOYLAMINO}-PENTANEDIOIC+ACID'>LYA</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=UMP:2-DEOXYURIDINE+5-MONOPHOSPHATE'>UMP</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1jtq\|1jtq]], [[1jtu\|1jtu]], [[1juj\|1juj]], [[1jut\|1jut]]</td></tr>
		+	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thymidylate_synthase Thymidylate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.45 2.1.1.45] </span></td></tr>
		+	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ju6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ju6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1ju6 RCSB], [http://www.ebi.ac.uk/pdbsum/1ju6 PDBsum]</span></td></tr>
		+	<table>
		+	== Evolutionary Conservation ==
		+	[[Image:Consurf_key_small.gif\|200px\|right]]
		+	Check<jmol>
		+	<jmolCheckbox>
		+	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ju/1ju6_consurf.spt"</scriptWhenChecked>
		+	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
		+	<text>to colour the structure by Evolutionary Conservation</text>
		+	</jmolCheckbox>
		+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
		+	<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Crystal structures of four pyrrolo(2,3-d)pyrimidine-based antifolate compounds, developed as inhibitors of thymidylate synthase (TS) in a strategy to circumvent drug-resistance, have been determined in complexes with their in vivo target, human thymidylate synthase, and with the structurally best-characterized Escherichia coli enzyme, to resolutions of 2.2-3.0 A. The 2.9 A crystal structure of a complex of human TS with one of the inhibitors, the multi-targeted antifolate LY231514, demonstrates that this compound induces a "closed" enzyme conformation and leads to formation of a covalent bond between enzyme and substrate. This structure is one of the first liganded human TS structures, and its solution was aided by mutation to facilitate crystallization. Structures of three other pyrrolo(2,3-d)pyrimidine-based antifolates in complex with Escherichia coli TS confirm the orientation of this class of inhibitors in the active site. Specific interactions between the polyglutamyl moiety and a positively charged groove on the enzyme surface explain the marked increase in affinity of the pyrrolo(2,3-d)pyrimidine inhibitors once they are polyglutamylated, as mediated in vivo by the cellular enzyme folyl polyglutamate synthetase.

-	~~{{STRUCTURE_1ju6\| PDB=1ju6 \| SCENE= }}~~	+	Multi-targeted antifolates aimed at avoiding drug resistance form covalent closed inhibitory complexes with human and Escherichia coli thymidylate synthases.,Sayre PH, Finer-Moore JS, Fritz TA, Biermann D, Gates SB, MacKellar WC, Patel VF, Stroud RM J Mol Biol. 2001 Nov 2;313(4):813-29. PMID:11697906<ref>PMID:11697906</ref>

-	~~===Human Thymidylate Synthase Complex with dUMP and LY231514~~, ~~A Pyrrolo(2,3-d)pyrimidine-based Antifolate===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_11697906}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[1ju6]] is~~ a ~~4 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=1JU6 OCA].~~	+

	==See Also==		==See Also==
	*[[Thymidylate synthase\|Thymidylate synthase]]		*[[Thymidylate synthase\|Thymidylate synthase]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<~~ref group="xtra">PMID:011697906<~~/~~ref~~><~~references group="xtra"~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Thymidylate synthase]]		[[Category: Thymidylate synthase]]

OCA at 12:44, 20 October 2012

OCA — Sat, 20 Oct 2012 12:44:01 GMT

←Older revision		Revision as of 12:44, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[1ju6]] is a 4 chain structure ~~of [[Thymidylate synthase]]~~ 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=1JU6 OCA].	+	[[1ju6]] is a 4 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=1JU6 OCA].

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

OCA: Protected "1ju6" [edit=sysop:move=sysop]

OCA — Thu, 26 Jul 2012 09:42:38 GMT

Protected "1ju6" [edit=sysop:move=sysop]

←Older revision

Revision as of 09:42, 26 July 2012