1hvy
From Proteopedia
(New page: 200px<br /> <applet load="1hvy" size="450" color="white" frame="true" align="right" spinBox="true" caption="1hvy, resolution 1.90Å" /> '''Human thymidylate s...) |
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| - | [[Image:1hvy.gif|left|200px]]<br /> | + | [[Image:1hvy.gif|left|200px]]<br /><applet load="1hvy" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1hvy" size=" | + | |
caption="1hvy, resolution 1.90Å" /> | caption="1hvy, resolution 1.90Å" /> | ||
'''Human thymidylate synthase complexed with dUMP and Raltitrexed, an antifolate drug, is in the closed conformation'''<br /> | '''Human thymidylate synthase complexed with dUMP and Raltitrexed, an antifolate drug, is in the closed conformation'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Thymidylate synthase (TS) is a major target in the chemotherapy of | + | 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== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 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 D16, UMP and BME 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:// | + | 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]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Thymidylate synthase]] | [[Category: Thymidylate synthase]] | ||
| - | [[Category: Berger, S | + | [[Category: Berger, S H.]] |
| - | [[Category: Dunlap, R | + | [[Category: Dunlap, R B.]] |
[[Category: Koli, S.]] | [[Category: Koli, S.]] | ||
[[Category: Lebioda, L.]] | [[Category: Lebioda, L.]] | ||
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[[Category: tomudex]] | [[Category: tomudex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:05:23 2008'' |
Revision as of 11:05, 21 February 2008
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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 disease associated with this structure: Timothy syndrome OMIM:[114205]
About this Structure
1HVY is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as Thymidylate synthase, with EC number 2.1.1.45 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
Page seeded by OCA on Thu Feb 21 13:05:23 2008
Categories: Homo sapiens | Single protein | Thymidylate synthase | Berger, S H. | Dunlap, R B. | Koli, S. | Lebioda, L. | Minor, W. | Phan, J. | BME | D16 | UMP | Raltitrexed | Tomudex
