1hvy

From Proteopedia

(Difference between revisions)

Revision as of 22:41, 10 September 2015

Human thymidylate synthase complexed with dUMP and Raltitrexed, an antifolate drug, is in the closed conformation

Structural highlights

1hvy is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
NonStd Res:
Activity:	Thymidylate synthase, with EC number 2.1.1.45
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[TYSY_HUMAN] Contributes to the de novo mitochondrial thymidylate biosynthesis pathway.^[1]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Thymidylate synthase (TS) is a major target in the chemotherapy of colorectal cancer and some other neoplasms while raltitrexed (Tomudex, ZD1694) is an antifolate inhibitor of TS approved for clinical use in several European countries. The crystal structure of the complex between recombinant human TS, dUMP, and raltitrexed has been determined at 1.9 A resolution. In contrast to the situation observed in the analogous complex of the rat TS, the enzyme is in the closed conformation and a covalent bond between the catalytic Cys 195 and dUMP is present in both subunits. This mode of ligand binding is similar to that of the analogous complex of the Escherichia coli enzyme. The only major differences observed are a direct hydrogen bond between His 196 and the O4 atom of dUMP and repositioning of the side chain of Tyr 94 by about 2 A. The thiophene ring of the drug is disordered between two parallel positions.

Human thymidylate synthase is in the closed conformation when complexed with dUMP and raltitrexed, an antifolate drug.,Phan J, Koli S, Minor W, Dunlap RB, Berger SH, Lebioda L Biochemistry. 2001 Feb 20;40(7):1897-902. PMID:11329255^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Anderson DD, Quintero CM, Stover PJ. Identification of a de novo thymidylate biosynthesis pathway in mammalian mitochondria. Proc Natl Acad Sci U S A. 2011 Sep 13;108(37):15163-8. doi:, 10.1073/pnas.1103623108. Epub 2011 Aug 26. PMID:21876188 doi:10.1073/pnas.1103623108
↑ Phan J, Koli S, Minor W, Dunlap RB, Berger SH, Lebioda L. Human thymidylate synthase is in the closed conformation when complexed with dUMP and raltitrexed, an antifolate drug. Biochemistry. 2001 Feb 20;40(7):1897-902. PMID:11329255

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1hvy"

@@ Line 2: / Line 2: @@
 <StructureSection load='1hvy' size='340' side='right' caption='[[1hvy]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1hvy]] 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=1HVY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1HVY FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1hvy]] 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=1HVY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1HVY FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=D16:TOMUDEX'>D16</scene>, <scene name='pdbligand=UMP:2-DEOXYURIDINE+5-MONOPHOSPHATE'>UMP</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='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=1hvy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hvy OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1hvy RCSB], [http://www.ebi.ac.uk/pdbsum/1hvy 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=1hvy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hvy OCA], [http://pdbe.org/1hvy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1hvy RCSB], [http://www.ebi.ac.uk/pdbsum/1hvy PDBsum]</span></td></tr>
 </table>
 == Function ==
@@ Line 28: / Line 28: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 1hvy" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 35: / Line 36: @@
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Thymidylate synthase]]
 [[Category: Berger, S H]]

1hvy

From Proteopedia

Revision as of 22:41, 10 September 2015

Human thymidylate synthase complexed with dUMP and Raltitrexed, an antifolate drug, is in the closed conformation

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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