1tsd: Difference between revisions

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[[Image:1tsd.~~gif~~|left|200px]]

[[Image:1tsd.png|left|200px]]

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~~'''~~THYMIDYLATE SYNTHASE COMPLEX WITH 2'-DEOXYURIDINE 5'-MONOPHOSPHATE (DUMP) AND FOLATE ANALOG 1843U89~~'''~~

===THYMIDYLATE SYNTHASE COMPLEX WITH 2'-DEOXYURIDINE 5'-MONOPHOSPHATE (DUMP) AND FOLATE ANALOG 1843U89===

~~==Overview==~~

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The anticancer drug 1843U89 inhibits thymidylate synthase (TS) at sub-nanomolar concentrations and is undergoing clinical trial. The 1.95 A crystal structure of Escherichia coli TS bound to the drug and dUMP reveals that the 1843U89 binding surface includes a hydrophobic patch that is normally buried. To reach this ~~patch~~, ~~1843U89 inserts into the wall of the TS active site~~, ~~resulting in a severe local distortion of~~ the ~~protein. In this new conformation, active-site groups that normally bind~~ to the ~~catalytic cofactor methylene-tetrahydrofolate instead bind to 1843U89 in new ways~~. ~~This structure provides a rare example of a protein that can bind tightly to distinct substances using a single~~, ~~flexible, binding surface~~. ~~This has implications for drug design, as 1843U89 could not have been obtained from current structure~~-~~based approaches.~~

The line below this paragraph, {{ABSTRACT_PUBMED_8846221}}, adds the Publication Abstract to the page

(as it appears on PubMed at http://www.pubmed.gov), where 8846221 is the PubMed ID number.

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==About this Structure==

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[[Category: 1843u89]]

[[Category: Dump]]

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Sat May 3 10~~:18:39 2008''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 00:15:53 2008''

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-[[Image:1tsd.gif|left|200px]]
+{{Seed}}
+[[Image:1tsd.png|left|200px]]
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 {{STRUCTURE_1tsd|  PDB=1tsd  |  SCENE=  }}
-'''THYMIDYLATE SYNTHASE COMPLEX WITH 2'-DEOXYURIDINE 5'-MONOPHOSPHATE (DUMP) AND FOLATE ANALOG 1843U89'''
+===THYMIDYLATE SYNTHASE COMPLEX WITH 2'-DEOXYURIDINE 5'-MONOPHOSPHATE (DUMP) AND FOLATE ANALOG 1843U89===
-==Overview==
+<!--
-The anticancer drug 1843U89 inhibits thymidylate synthase (TS) at sub-nanomolar concentrations and is undergoing clinical trial. The 1.95 A crystal structure of Escherichia coli TS bound to the drug and dUMP reveals that the 1843U89 binding surface includes a hydrophobic patch that is normally buried. To reach this patch, 1843U89 inserts into the wall of the TS active site, resulting in a severe local distortion of the protein. In this new conformation, active-site groups that normally bind to the catalytic cofactor methylene-tetrahydrofolate instead bind to 1843U89 in new ways. This structure provides a rare example of a protein that can bind tightly to distinct substances using a single, flexible, binding surface. This has implications for drug design, as 1843U89 could not have been obtained from current structure-based approaches.
+The line below this paragraph, {{ABSTRACT_PUBMED_8846221}}, adds the Publication Abstract to the page
+(as it appears on PubMed at http://www.pubmed.gov), where 8846221 is the PubMed ID number.
+-->
+{{ABSTRACT_PUBMED_8846221}}
 ==About this Structure==
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 [[Category: 1843u89]]
 [[Category: Dump]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 10:18:39 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 00:15:53 2008''