1tsd

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

spinqualitylabelsall models 1tsd, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1tsd is a 2 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: BME, F89, UMP NonStd Res: FMT Activity: Thymidylate synthase, with EC number 2.1.1.45 Resources: FirstGlance, OCA, RCSB, PDBsum 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 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. Ligand-induced distortion of an active site in thymidylate synthase upon binding anticancer drug 1843U89.,Weichsel A, Montfort WR Nat Struct Biol. 1995 Dec;2(12):1095-101. PMID:8846221 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Thymidylate synthase

Proteopedia Page Contributors and Editors (what is this?)

OCA