Structural highlights
Function
[TYSY_ECOLI] Provides the sole de novo source of dTMP for DNA biosynthesis. This protein also binds to its mRNA thus repressing its own translation.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Weichsel A, Montfort WR. Ligand-induced distortion of an active site in thymidylate synthase upon binding anticancer drug 1843U89. Nat Struct Biol. 1995 Dec;2(12):1095-101. PMID:8846221
