1hw3 - Revision history

OCA at 11:35, 27 March 2024

OCA — Wed, 27 Mar 2024 11:35:37 GMT

←Older revision		Revision as of 11:35, 27 March 2024
Line 3:		Line 3:
	<StructureSection load='1hw3' size='340' side='right'caption='[[1hw3]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='1hw3' size='340' side='right'caption='[[1hw3]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1hw3]] is a 1 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=1HW3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HW3 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1hw3]] is a 1 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=1HW3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HW3 FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=EDO:1~~,2~~-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2Å</td></tr>
-	<tr id='~~NonStdRes~~'><td class="sblockLbl"><b>[[~~Non-Standard_Residue~~\|~~NonStd Res~~:]]</b></td><td class="sblockDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene><~~/td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	~~<tr id~~='~~related'><td class~~=~~"sblockLbl"><b>[[Related_structure\|Related~~:~~]]</b></td><td class="sblockDat"><div style='overflow: auto; max~~-~~height: 3em;~~'>~~[[1hw4\|1hw4]]~~</~~div~~><~~/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=1hw3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hw3 OCA], [https://pdbe.org/1hw3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hw3 RCSB], [https://www.ebi.ac.uk/pdbsum/1hw3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hw3 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=1hw3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hw3 OCA], [https://pdbe.org/1hw3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hw3 RCSB], [https://www.ebi.ac.uk/pdbsum/1hw3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hw3 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 22:		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=1hw3 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=1hw3 ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Thymidylate synthase (TS) is a major target in the chemotherapy of colorectal cancer and some other neoplasms. The emergence of resistance to the treatment is often related to the increased levels of TS in cancer cells, which have been linked to the elimination of TS binding to its own mRNA upon drug binding, a feedback regulatory mechanism, and/or to the increased stability to intracellular degradation of TS.drug complexes (versus unliganded TS). The active site loop of human TS (hTS) has a unique conformation resulted from a rotation by 180 degrees relative to its orientation in bacterial TSs. In this conformation, the enzyme must be inactive, because the catalytic cysteine is no longer positioned in the ligand-binding pocket. The ordered solvent structure obtained from high resolution crystallographic data (2.0 A) suggests that the inactive loop conformation promotes mRNA binding and intracellular degradation of the enzyme. This hypothesis is supported by fluorescence studies, which indicate that in solution both active and inactive forms of hTS are present. The binding of phosphate ion shifts the equilibrium toward the inactive conformation; subsequent dUMP binding reverses the equilibrium toward the active form. Thus, TS inhibition via stabilization of the inactive conformation should lead to less resistance than is observed with presently used drugs, which are analogs of its substrates, dUMP and CH(2)H(4)folate, and bind in the active site, promoting the active conformation. The presence of an extension at the N terminus of native hTS has no significant effect on kinetic properties or crystal structure.
-
-	Structure of human thymidylate synthase suggests advantages of chemotherapy with noncompetitive inhibitors.,Phan J, Steadman DJ, Koli S, Ding WC, Minor W, Dunlap RB, Berger SH, Lebioda L J Biol Chem. 2001 Apr 27;276(17):14170-7. Epub 2001 Jan 24. PMID:11278511<ref>PMID:11278511</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 1hw3" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 38:		Line 27:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Thymidylate synthase]]~~	+	[[Category: Berger SH]]
-	[[Category: Berger~~, S H~~]]	+	[[Category: Ding WC]]
-	[[Category: Ding~~, W C~~]]	+	[[Category: Dunlap RB]]
-	[[Category: Dunlap~~, R B~~]]	+	[[Category: Koli S]]
-	[[Category: Koli, S]]	+	[[Category: Lebioda L]]
-	[[Category: Lebioda, L]]	+	[[Category: Minor W]]
-	[[Category: Minor, W]]	+	[[Category: Phan J]]
-	[[Category: Phan, J]]	+	[[Category: Steadman JD]]
-	[[Category: Steadman~~, J D]]~~	+
-	~~[[Category: Methyltransferase]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 09:51, 13 April 2022

OCA — Wed, 13 Apr 2022 09:51:07 GMT

←Older revision		Revision as of 09:51, 13 April 2022
Line 3:		Line 3:
	<StructureSection load='1hw3' size='340' side='right'caption='[[1hw3]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='1hw3' size='340' side='right'caption='[[1hw3]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1hw3]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HW3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HW3 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1hw3]] is a 1 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=1HW3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HW3 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene></td></tr>
Line 38:		Line 38:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Thymidylate synthase]]		[[Category: Thymidylate synthase]]

OCA at 07:29, 7 April 2021

OCA — Wed, 07 Apr 2021 07:29:45 GMT

←Older revision		Revision as of 07:29, 7 April 2021
Line 3:		Line 3:
	<StructureSection load='1hw3' size='340' side='right'caption='[[1hw3]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='1hw3' size='340' side='right'caption='[[1hw3]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1hw3]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HW3 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=1HW3 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1hw3]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HW3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HW3 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1hw4\|1hw4]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1hw4\|1hw4]]</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=1hw3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hw3 OCA], [~~http~~://pdbe.org/1hw3 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=1hw3 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/1hw3 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=1hw3 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=1hw3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hw3 OCA], [https://pdbe.org/1hw3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hw3 RCSB], [https://www.ebi.ac.uk/pdbsum/1hw3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hw3 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 33:		Line 33:

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

OCA at 07:50, 3 July 2019

OCA — Wed, 03 Jul 2019 07:50:18 GMT

←Older revision		Revision as of 07:50, 3 July 2019
Line 1:		Line 1:

	==STRUCTURE OF HUMAN THYMIDYLATE SYNTHASE SUGGESTS ADVANTAGES OF CHEMOTHERAPY WITH NONCOMPETITIVE INHIBITORS==		==STRUCTURE OF HUMAN THYMIDYLATE SYNTHASE SUGGESTS ADVANTAGES OF CHEMOTHERAPY WITH NONCOMPETITIVE INHIBITORS==
-	<StructureSection load='1hw3' size='340' side='right' caption='[[1hw3]], [[Resolution\|resolution]] 2.00Å' scene=''>	+	<StructureSection load='1hw3' size='340' side='right'caption='[[1hw3]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1hw3]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HW3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1HW3 FirstGlance]. <br>		<table><tr><td colspan='2'>[[1hw3]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HW3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1HW3 FirstGlance]. <br>
Line 16:		Line 16:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hw/1hw3_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hw/1hw3_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 38:		Line 38:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Thymidylate synthase]]		[[Category: Thymidylate synthase]]
	[[Category: Berger, S H]]		[[Category: Berger, S H]]

OCA at 10:50, 27 September 2017

OCA — Wed, 27 Sep 2017 10:50:37 GMT

←Older revision		Revision as of 10:50, 27 September 2017
Line 1:		Line 1:
		+
	==STRUCTURE OF HUMAN THYMIDYLATE SYNTHASE SUGGESTS ADVANTAGES OF CHEMOTHERAPY WITH NONCOMPETITIVE INHIBITORS==		==STRUCTURE OF HUMAN THYMIDYLATE SYNTHASE SUGGESTS ADVANTAGES OF CHEMOTHERAPY WITH NONCOMPETITIVE INHIBITORS==
	<StructureSection load='1hw3' size='340' side='right' caption='[[1hw3]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='1hw3' size='340' side='right' caption='[[1hw3]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1hw3]] is a 1 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=1HW3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1HW3 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1hw3]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HW3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1HW3 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1hw4\|1hw4]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1hw4\|1hw4]]</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=1hw3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hw3 OCA], [http://pdbe.org/1hw3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1hw3 RCSB], [http://www.ebi.ac.uk/pdbsum/1hw3 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=1hw3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hw3 OCA], [http://pdbe.org/1hw3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1hw3 RCSB], [http://www.ebi.ac.uk/pdbsum/1hw3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1hw3 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 20:
	<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=1hw3 ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 37:		Line 38:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Human]]
	[[Category: Thymidylate synthase]]		[[Category: Thymidylate synthase]]
	[[Category: Berger, S H]]		[[Category: Berger, S H]]

OCA at 08:03, 11 September 2015

OCA — Fri, 11 Sep 2015 08:03:49 GMT

←Older revision		Revision as of 08:03, 11 September 2015
Line 2:		Line 2:
	<StructureSection load='1hw3' size='340' side='right' caption='[[1hw3]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='1hw3' size='340' side='right' caption='[[1hw3]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1hw3]] is a 1 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=1HW3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1HW3 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1hw3]] is a 1 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=1HW3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1HW3 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1hw4\|1hw4]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1hw4\|1hw4]]</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=1hw3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hw3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1hw3 RCSB], [http://www.ebi.ac.uk/pdbsum/1hw3 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=1hw3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hw3 OCA], [http://pdbe.org/1hw3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1hw3 RCSB], [http://www.ebi.ac.uk/pdbsum/1hw3 PDBsum]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 29:		Line 29:
	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 1hw3" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 36:		Line 37:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Thymidylate synthase]]		[[Category: Thymidylate synthase]]
	[[Category: Berger, S H]]		[[Category: Berger, S H]]

OCA at 13:36, 25 December 2014

OCA — Thu, 25 Dec 2014 13:36:44 GMT

←Older revision		Revision as of 13:36, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1hw3]] is a 1 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=1HW3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1HW3 FirstGlance]. <br>		<table><tr><td colspan='2'>[[1hw3]] is a 1 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=1HW3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1HW3 FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene></td></tr>	+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1hw4\|1hw4]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1hw4\|1hw4]]</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=1hw3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hw3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1hw3 RCSB], [http://www.ebi.ac.uk/pdbsum/1hw3 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=1hw3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hw3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1hw3 RCSB], [http://www.ebi.ac.uk/pdbsum/1hw3 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 36:		Line 38:
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Thymidylate synthase]]		[[Category: Thymidylate synthase]]
-	[[Category: Berger, S H.]]	+	[[Category: Berger, S H]]
-	[[Category: Ding, W C.]]	+	[[Category: Ding, W C]]
-	[[Category: Dunlap, R B.]]	+	[[Category: Dunlap, R B]]
-	[[Category: Koli, S.]]	+	[[Category: Koli, S]]
-	[[Category: Lebioda, L.]]	+	[[Category: Lebioda, L]]
-	[[Category: Minor, W.]]	+	[[Category: Minor, W]]
-	[[Category: Phan, J.]]	+	[[Category: Phan, J]]
-	[[Category: Steadman, J D.]]	+	[[Category: Steadman, J D]]
	[[Category: Methyltransferase]]		[[Category: Methyltransferase]]
-	[[Category: Thymidylate synthase]]
	[[Category: Transferase]]		[[Category: Transferase]]

OCA at 12:14, 28 September 2014

OCA — Sun, 28 Sep 2014 12:14:03 GMT

←Older revision		Revision as of 12:14, 28 September 2014
Line 1:		Line 1:
-	[[~~Image:~~1hw3.~~png~~\|~~left~~\|200px]]	+	==STRUCTURE OF HUMAN THYMIDYLATE SYNTHASE SUGGESTS ADVANTAGES OF CHEMOTHERAPY WITH NONCOMPETITIVE INHIBITORS==
		+	<StructureSection load='1hw3' size='340' side='right' caption='[[1hw3]], [[Resolution\|resolution]] 2.00Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[1hw3]] is a 1 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=1HW3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1HW3 FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene></td></tr>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1hw4\|1hw4]]</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=1hw3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hw3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1hw3 RCSB], [http://www.ebi.ac.uk/pdbsum/1hw3 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/hw/1hw3_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 ==
		+	Thymidylate synthase (TS) is a major target in the chemotherapy of colorectal cancer and some other neoplasms. The emergence of resistance to the treatment is often related to the increased levels of TS in cancer cells, which have been linked to the elimination of TS binding to its own mRNA upon drug binding, a feedback regulatory mechanism, and/or to the increased stability to intracellular degradation of TS.drug complexes (versus unliganded TS). The active site loop of human TS (hTS) has a unique conformation resulted from a rotation by 180 degrees relative to its orientation in bacterial TSs. In this conformation, the enzyme must be inactive, because the catalytic cysteine is no longer positioned in the ligand-binding pocket. The ordered solvent structure obtained from high resolution crystallographic data (2.0 A) suggests that the inactive loop conformation promotes mRNA binding and intracellular degradation of the enzyme. This hypothesis is supported by fluorescence studies, which indicate that in solution both active and inactive forms of hTS are present. The binding of phosphate ion shifts the equilibrium toward the inactive conformation; subsequent dUMP binding reverses the equilibrium toward the active form. Thus, TS inhibition via stabilization of the inactive conformation should lead to less resistance than is observed with presently used drugs, which are analogs of its substrates, dUMP and CH(2)H(4)folate, and bind in the active site, promoting the active conformation. The presence of an extension at the N terminus of native hTS has no significant effect on kinetic properties or crystal structure.

-	~~{{STRUCTURE_1hw3\| PDB=1hw3 \| SCENE= }}~~	+	Structure of human thymidylate synthase suggests advantages of chemotherapy with noncompetitive inhibitors.,Phan J, Steadman DJ, Koli S, Ding WC, Minor W, Dunlap RB, Berger SH, Lebioda L J Biol Chem. 2001 Apr 27;276(17):14170-7. Epub 2001 Jan 24. PMID:11278511<ref>PMID:11278511</ref>

-	~~===STRUCTURE OF HUMAN THYMIDYLATE SYNTHASE SUGGESTS ADVANTAGES OF CHEMOTHERAPY WITH NONCOMPETITIVE INHIBITORS===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_11278511}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[1hw3]] is~~ a ~~1 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=1HW3 OCA].~~	+

	==See Also==		==See Also==
	*[[Thymidylate synthase\|Thymidylate synthase]]		*[[Thymidylate synthase\|Thymidylate synthase]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<~~ref group="xtra">PMID:011278511<~~/~~ref~~><~~references group="xtra"~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Thymidylate synthase]]		[[Category: Thymidylate synthase]]

OCA at 17:19, 20 October 2012

OCA — Sat, 20 Oct 2012 17:19:29 GMT

←Older revision		Revision as of 17:19, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[1hw3]] is a 1 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=1HW3 OCA].	+	[[1hw3]] is a 1 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=1HW3 OCA].

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

OCA: Protected "1hw3" [edit=sysop:move=sysop]

OCA — Fri, 27 Jul 2012 00:32:47 GMT

Protected "1hw3" [edit=sysop:move=sysop]

←Older revision

Revision as of 00:32, 27 July 2012