1hvy

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[[Image:1hvy.gif|left|200px]]<br /><applet load="1hvy" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1hvy.gif|left|200px]]
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caption="1hvy, resolution 1.90&Aring;" />
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'''Human thymidylate synthase complexed with dUMP and Raltitrexed, an antifolate drug, is in the closed conformation'''<br />
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{{Structure
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|PDB= 1hvy |SIZE=350|CAPTION= <scene name='initialview01'>1hvy</scene>, resolution 1.90&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=D16:TOMUDEX'>D16</scene>, <scene name='pdbligand=UMP:2'-DEOXYURIDINE+5'-MONOPHOSPHATE'>UMP</scene> and <scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>
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|ACTIVITY= [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]
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|GENE=
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}}
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'''Human thymidylate synthase complexed with dUMP and Raltitrexed, an antifolate drug, is in the closed conformation'''
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==Overview==
==Overview==
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==Disease==
==Disease==
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Known disease associated with this structure: Timothy syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=114205 114205]]
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Known diseases associated with this structure: Brugada syndrome 3 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=114205 114205]], Timothy syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=114205 114205]]
==About this Structure==
==About this Structure==
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1HVY is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=D16:'>D16</scene>, <scene name='pdbligand=UMP:'>UMP</scene> and <scene name='pdbligand=BME:'>BME</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HVY OCA].
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1HVY is a [[Single protein]] structure of 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].
==Reference==
==Reference==
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11329255 11329255]
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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:[http://www.ncbi.nlm.nih.gov/pubmed/11329255 11329255]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: tomudex]]
[[Category: tomudex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:05:23 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:42:17 2008''

Revision as of 09:42, 20 March 2008

Image:1hvy.gif


PDB ID 1hvy

Drag the structure with the mouse to rotate
, resolution 1.90Å
Ligands: , and
Activity: Thymidylate synthase, with EC number 2.1.1.45
Coordinates: save as pdb, mmCIF, xml



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


Contents

Overview

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.

Disease

Known diseases associated with this structure: Brugada syndrome 3 OMIM:[114205], Timothy syndrome OMIM:[114205]

About this Structure

1HVY is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

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

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