4e28 - Revision history

OCA at 02:48, 21 November 2024

2024-11-21T02:48:56Z

← Older revision		Revision as of 02:48, 21 November 2024
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	== 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>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Human thymidylate synthase (hTS) was targeted through a virtual screening approach. The most optimal inhibitor identified, 2-{4-hydroxy-2-[(2-hydroxybenzylidene)hydrazono]-2,5-dihydrothiazol-5-yl}-N-(3-tr ifluoromethylphenyl)acetamide (5), showed a mixed-type inhibition pattern, with a K(i) of 1.3 muM and activity against ovarian cancer cell lines with the same potency as cisplatin. X-ray studies revealed that it binds the inactive enzyme conformation. This study is the first example of a nonpeptidic inhibitor that binds the inactive hTS and exhibits anticancer activity against ovarian cancer cells.

			Inhibitor of Ovarian Cancer Cells Growth by Virtual Screening: A New Thiazole Derivative Targeting Human Thymidylate Synthase.,Carosati E, Tochowicz A, Marverti G, Guaitoli G, Benedetti P, Ferrari S, Stroud RM, Finer-Moore J, Luciani R, Farina D, Cruciani G, Costi MP J Med Chem. 2012 Nov 5. PMID:23075414<ref>PMID:23075414</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 4e28" style="background-color:#fffaf0;"></div>

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

OCA at 14:50, 14 March 2024

2024-03-14T14:50:11Z

← Older revision		Revision as of 14:50, 14 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4e28]] 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=4E28 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E28 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4e28]] 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=4E28 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E28 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0MZ:2-{(2Z,5S)-4-HYDROXY-2-[(2E)-(2-HYDROXYBENZYLIDENE)HYDRAZINYLIDENE]-2,5-DIHYDRO-1,3-THIAZOL-5-YL}-N-[3-(TRIFLUOROMETHYL)PHENYL]ACETAMIDE'>0MZ</scene>, <scene name='pdbligand=9MZ:2-{(5S)-2-[(2E)-2-(2-HYDROXYBENZYLIDENE)HYDRAZINYL]-4-OXO-4,5-DIHYDRO-1,3-THIAZOL-5-YL}-N-[3-(TRIFLUOROMETHYL)PHENYL]ACETAMIDE'>9MZ</scene>, <scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</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]] 2.302Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0MZ:2-{(2Z,5S)-4-HYDROXY-2-[(2E)-(2-HYDROXYBENZYLIDENE)HYDRAZINYLIDENE]-2,5-DIHYDRO-1,3-THIAZOL-5-YL}-N-[3-(TRIFLUOROMETHYL)PHENYL]ACETAMIDE'>0MZ</scene>, <scene name='pdbligand=9MZ:2-{(5S)-2-[(2E)-2-(2-HYDROXYBENZYLIDENE)HYDRAZINYL]-4-OXO-4,5-DIHYDRO-1,3-THIAZOL-5-YL}-N-[3-(TRIFLUOROMETHYL)PHENYL]ACETAMIDE'>9MZ</scene>, <scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4e28 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e28 OCA], [https://pdbe.org/4e28 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e28 RCSB], [https://www.ebi.ac.uk/pdbsum/4e28 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e28 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=4e28 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e28 OCA], [https://pdbe.org/4e28 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e28 RCSB], [https://www.ebi.ac.uk/pdbsum/4e28 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e28 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>
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	Human thymidylate synthase (hTS) was targeted through a virtual screening approach. The most optimal inhibitor identified, 2-{4-hydroxy-2-[(2-hydroxybenzylidene)hydrazono]-2,5-dihydrothiazol-5-yl}-N-(3-tr ifluoromethylphenyl)acetamide (5), showed a mixed-type inhibition pattern, with a K(i) of 1.3 muM and activity against ovarian cancer cell lines with the same potency as cisplatin. X-ray studies revealed that it binds the inactive enzyme conformation. This study is the first example of a nonpeptidic inhibitor that binds the inactive hTS and exhibits anticancer activity against ovarian cancer cells.

	Inhibitor of Ovarian Cancer Cells Growth by Virtual Screening: A New Thiazole Derivative Targeting Human Thymidylate Synthase.,Carosati E, Tochowicz A, Marverti G, Guaitoli G, Benedetti P, Ferrari S, Stroud RM, Finer-Moore J, Luciani R, Farina D, Cruciani G, Costi MP J Med Chem. 2012 Nov 5. PMID:23075414<ref>PMID:23075414</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 4e28" style="background-color:#fffaf0;"></div~~>

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

OCA at 06:45, 28 September 2022

2022-09-28T06:45:54Z

← Older revision		Revision as of 06:45, 28 September 2022
Line 1:		Line 1:

	==Structure of human thymidylate synthase in inactive conformation with a novel non-peptidic inhibitor==		==Structure of human thymidylate synthase in inactive conformation with a novel non-peptidic inhibitor==
	<StructureSection load='4e28' size='340' side='right' caption='[[4e28]], [[Resolution\|resolution]] 2.30Å' scene=''>		<StructureSection load='4e28' size='340' side='right'caption='[[4e28]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4e28]] 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=4E28 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4E28 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4e28]] 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=4E28 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E28 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0MZ:2-{(2Z,5S)-4-HYDROXY-2-[(2E)-(2-HYDROXYBENZYLIDENE)HYDRAZINYLIDENE]-2,5-DIHYDRO-1,3-THIAZOL-5-YL}-N-[3-(TRIFLUOROMETHYL)PHENYL]ACETAMIDE'>0MZ</scene>, <scene name='pdbligand=9MZ:2-{(5S)-2-[(2E)-2-(2-HYDROXYBENZYLIDENE)HYDRAZINYL]-4-OXO-4,5-DIHYDRO-1,3-THIAZOL-5-YL}-N-[3-(TRIFLUOROMETHYL)PHENYL]ACETAMIDE'>9MZ</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=0MZ:2-{(2Z,5S)-4-HYDROXY-2-[(2E)-(2-HYDROXYBENZYLIDENE)HYDRAZINYLIDENE]-2,5-DIHYDRO-1,3-THIAZOL-5-YL}-N-[3-(TRIFLUOROMETHYL)PHENYL]ACETAMIDE'>0MZ</scene>, <scene name='pdbligand=9MZ:2-{(5S)-2-[(2E)-2-(2-HYDROXYBENZYLIDENE)HYDRAZINYL]-4-OXO-4,5-DIHYDRO-1,3-THIAZOL-5-YL}-N-[3-(TRIFLUOROMETHYL)PHENYL]ACETAMIDE'>9MZ</scene>, <scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4e28 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e28 OCA], [https://pdbe.org/4e28 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e28 RCSB], [https://www.ebi.ac.uk/pdbsum/4e28 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e28 ProSAT]</span></td></tr>
	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3egy\|3egy]]~~, ~~[[3ehi\|3ehi]]~~<~~/td></tr>~~
	~~<tr id~~='~~gene'><td class~~=~~"sblockLbl"><b>[[Gene\|Gene~~:~~]]</b></td><td class="sblockDat">TYMS, TS, OK/SW-cl.29 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>~~
	~~<tr id='activity~~'>~~<td class="sblockLbl"><b>Activity:~~</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/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=4e28 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e28 OCA], [~~http~~://pdbe.org/4e28 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4e28 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4e28 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4e28 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>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 22:		Line 18:
	</div>		</div>
	<div class="pdbe-citations 4e28" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4e28" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Thymidylate synthase 3D structures\|Thymidylate synthase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: ~~Thymidylate synthase~~]]		[[Category: Large Structures]]
	[[Category: Costi~~, M P~~]]		[[Category: Costi MP]]
	[[Category: Finer-Moore, J]]		[[Category: Finer-Moore J]]
	[[Category: Stroud~~, R M~~]]		[[Category: Stroud RM]]
	[[Category: Tochowicz, A]]		[[Category: Tochowicz A]]
	~~[[Category: Hts-inhibitor complex]]~~
	~~[[Category: Transferase-transferase inhibitor complex~~]]

OCA at 07:58, 15 November 2017

2017-11-15T07:58:46Z

← Older revision		Revision as of 07:58, 15 November 2017
Line 22:		Line 22:
	</div>		</div>
	<div class="pdbe-citations 4e28" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4e28" style="background-color:#fffaf0;"></div>

	~~==See Also==~~
	*[[Thymidylate synthase\|Thymidylate synthase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 07:55, 4 August 2016

2016-08-04T07:55:52Z

← Older revision		Revision as of 07:55, 4 August 2016
Line 1:		Line 1:

	==Structure of human thymidylate synthase in inactive conformation with a novel non-peptidic inhibitor==		==Structure of human thymidylate synthase in inactive conformation with a novel non-peptidic inhibitor==
	<StructureSection load='4e28' size='340' side='right' caption='[[4e28]], [[Resolution\|resolution]] 2.30Å' scene=''>		<StructureSection load='4e28' size='340' side='right' caption='[[4e28]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4e28]] 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=4E28 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E28 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4e28]] 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=4E28 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E28 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0MZ:2-{(2Z,5S)-4-HYDROXY-2-[(2E)-(2-HYDROXYBENZYLIDENE)HYDRAZINYLIDENE]-2,5-DIHYDRO-1,3-THIAZOL-5-YL}-N-[3-(TRIFLUOROMETHYL)PHENYL]ACETAMIDE'>0MZ</scene>, <scene name='pdbligand=9MZ:2-{(5S)-2-[(2E)-2-(2-HYDROXYBENZYLIDENE)HYDRAZINYL]-4-OXO-4,5-DIHYDRO-1,3-THIAZOL-5-YL}-N-[3-(TRIFLUOROMETHYL)PHENYL]ACETAMIDE'>9MZ</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=0MZ:2-{(2Z,5S)-4-HYDROXY-2-[(2E)-(2-HYDROXYBENZYLIDENE)HYDRAZINYLIDENE]-2,5-DIHYDRO-1,3-THIAZOL-5-YL}-N-[3-(TRIFLUOROMETHYL)PHENYL]ACETAMIDE'>0MZ</scene>, <scene name='pdbligand=9MZ:2-{(5S)-2-[(2E)-2-(2-HYDROXYBENZYLIDENE)HYDRAZINYL]-4-OXO-4,5-DIHYDRO-1,3-THIAZOL-5-YL}-N-[3-(TRIFLUOROMETHYL)PHENYL]ACETAMIDE'>9MZ</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">[[3egy\|3egy]], [[3ehi\|3ehi]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3egy\|3egy]], [[3ehi\|3ehi]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TYMS, TS, OK/SW-cl.29 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TYMS, TS, OK/SW-cl.29 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/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=4e28 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e28 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4e28 RCSB], [http://www.ebi.ac.uk/pdbsum/4e28 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=4e28 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e28 OCA], [http://pdbe.org/4e28 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4e28 RCSB], [http://www.ebi.ac.uk/pdbsum/4e28 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4e28 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 20:		Line 21:
	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 4e28" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 27:		Line 29:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Homo sapiens~~]]		[[Category: Human]]
	[[Category: Thymidylate synthase]]		[[Category: Thymidylate synthase]]
	[[Category: Costi, M P]]		[[Category: Costi, M P]]

OCA at 07:16, 24 December 2014

2014-12-24T07:16:41Z

← Older revision		Revision as of 07:16, 24 December 2014
Line 10:		Line 10:
	<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=4e28 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e28 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4e28 RCSB], [http://www.ebi.ac.uk/pdbsum/4e28 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=4e28 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e28 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4e28 RCSB], [http://www.ebi.ac.uk/pdbsum/4e28 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>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 15:35, 9 December 2014

2014-12-09T15:35:52Z

← Older revision		Revision as of 15:35, 9 December 2014
Line 1:		Line 1:
	[[~~Image~~:~~4e28~~.~~png~~\|~~left~~\|~~200px~~]]		==Structure of human thymidylate synthase in inactive conformation with a novel non-peptidic inhibitor==
			<StructureSection load='4e28' size='340' side='right' caption='[[4e28]], [[Resolution\|resolution]] 2.30Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[4e28]] 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=4E28 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E28 FirstGlance]. <br>
			</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0MZ:2-{(2Z,5S)-4-HYDROXY-2-[(2E)-(2-HYDROXYBENZYLIDENE)HYDRAZINYLIDENE]-2,5-DIHYDRO-1,3-THIAZOL-5-YL}-N-[3-(TRIFLUOROMETHYL)PHENYL]ACETAMIDE'>0MZ</scene>, <scene name='pdbligand=9MZ:2-{(5S)-2-[(2E)-2-(2-HYDROXYBENZYLIDENE)HYDRAZINYL]-4-OXO-4,5-DIHYDRO-1,3-THIAZOL-5-YL}-N-[3-(TRIFLUOROMETHYL)PHENYL]ACETAMIDE'>9MZ</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='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3egy\|3egy]], [[3ehi\|3ehi]]</td></tr>
			<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TYMS, TS, OK/SW-cl.29 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=4e28 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e28 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4e28 RCSB], [http://www.ebi.ac.uk/pdbsum/4e28 PDBsum]</span></td></tr>
			</table>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Human thymidylate synthase (hTS) was targeted through a virtual screening approach. The most optimal inhibitor identified, 2-{4-hydroxy-2-[(2-hydroxybenzylidene)hydrazono]-2,5-dihydrothiazol-5-yl}-N-(3-tr ifluoromethylphenyl)acetamide (5), showed a mixed-type inhibition pattern, with a K(i) of 1.3 muM and activity against ovarian cancer cell lines with the same potency as cisplatin. X-ray studies revealed that it binds the inactive enzyme conformation. This study is the first example of a nonpeptidic inhibitor that binds the inactive hTS and exhibits anticancer activity against ovarian cancer cells.

	~~{{STRUCTURE_4e28\| PDB=4e28 \| SCENE= }}~~		Inhibitor of Ovarian Cancer Cells Growth by Virtual Screening: A New Thiazole Derivative Targeting Human Thymidylate Synthase.,Carosati E, Tochowicz A, Marverti G, Guaitoli G, Benedetti P, Ferrari S, Stroud RM, Finer-Moore J, Luciani R, Farina D, Cruciani G, Costi MP J Med Chem. 2012 Nov 5. PMID:23075414<ref>PMID:23075414</ref>

	~~===Structure~~ of ~~human thymidylate synthase in inactive conformation with a novel non-peptidic inhibitor===~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>

	~~{{ABSTRACT_PUBMED_23075414}}~~		==See Also==
			*[[Thymidylate synthase\|Thymidylate synthase]]
	==~~About this Structure~~==		== References ==
	[[~~4e28~~]] ~~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=4E28 OCA].~~		<references/>
			__TOC__
			</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Thymidylate synthase]]		[[Category: Thymidylate synthase]]
	[[Category: Costi, M P.]]		[[Category: Costi, M P]]
	[[Category: Finer-Moore, J.]]		[[Category: Finer-Moore, J]]
	[[Category: Stroud, R M.]]		[[Category: Stroud, R M]]
	[[Category: Tochowicz, A.]]		[[Category: Tochowicz, A]]
	[[Category: Hts-inhibitor complex]]		[[Category: Hts-inhibitor complex]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

OCA at 21:31, 12 December 2012

2012-12-12T21:31:50Z

← Older revision		Revision as of 21:31, 12 December 2012
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	[[Image:4e28.~~jpg~~\|left\|200px]]		[[Image:4e28.png\|left\|200px]]

	{{STRUCTURE_4e28\| PDB=4e28 \| SCENE= }}		{{STRUCTURE_4e28\| PDB=4e28 \| SCENE= }}
Line 5:		Line 5:
	===Structure of human thymidylate synthase in inactive conformation with a novel non-peptidic inhibitor===		===Structure of human thymidylate synthase in inactive conformation with a novel non-peptidic inhibitor===

			{{ABSTRACT_PUBMED_23075414}}

	==About this Structure==		==About this Structure==

OCA at 06:38, 14 November 2012

2012-11-14T06:38:27Z

← Older revision		Revision as of 06:38, 14 November 2012
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	~~'''Unreleased structure'''~~		[[Image:4e28.jpg\|left\|200px]]

	~~The entry~~ 4e28 ~~is ON HOLD~~ ~~until Paper Publication~~		{{STRUCTURE_4e28\| PDB=4e28 \| SCENE= }}

	~~Authors: Tochowicz, A., Finer~~-~~Moore, J., Stroud, R.M., Costi, M.P.~~		===Structure of human thymidylate synthase in inactive conformation with a novel non-peptidic inhibitor===

	~~Description~~: ~~Structure of human thymidylate~~ synthase ~~in inactive conformation with a novel non~~-~~peptidic~~ inhibitor
			==About this Structure==
			[[4e28]] 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=4E28 OCA].
			[[Category: Homo sapiens]]
			[[Category: Thymidylate synthase]]
			[[Category: Costi, M P.]]
			[[Category: Finer-Moore, J.]]
			[[Category: Stroud, R M.]]
			[[Category: Tochowicz, A.]]
			[[Category: Hts-inhibitor complex]]
			[[Category: Transferase-transferase inhibitor complex]]

OCA at 07:14, 21 March 2012

2012-03-21T07:14:49Z

← Older revision		Revision as of 07:14, 21 March 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 4e28 is ON HOLD		The entry 4e28 is ON HOLD until Paper Publication

	Authors: Tochowicz, A., Finer-Moore, J., Stroud, R.M. , Costi, M.P.		Authors: Tochowicz, A., Finer-Moore, J., Stroud, R.M., Costi, M.P.

	Description: Structure of ~~Human Thymidylate Synthase~~ in inactive conformation with a novel non-peptidic inhibitor		Description: Structure of human thymidylate synthase in inactive conformation with a novel non-peptidic inhibitor