1TSD
THYMIDYLATE SYNTHASE COMPLEX WITH 2'-DEOXYURIDINE 5'-MONOPHOSPHATE (DUMP) AND FOLATE ANALOG 1843U89
Summary for 1TSD
| Entry DOI | 10.2210/pdb1tsd/pdb |
| Descriptor | THYMIDYLATE SYNTHASE, BETA-MERCAPTOETHANOL, 2'-DEOXYURIDINE 5'-MONOPHOSPHATE, ... (5 entities in total) |
| Functional Keywords | dump, 1843u89, transferase (methyltransferase) |
| Biological source | Escherichia coli |
| Total number of polymer chains | 2 |
| Total formula weight | 62860.96 |
| Authors | Weichsel, A.,Montfort, W.R. (deposition date: 1995-08-15, release date: 1996-01-29, Last modification date: 2025-03-26) |
| Primary citation | Weichsel, A.,Montfort, W.R. Ligand-induced distortion of an active site in thymidylate synthase upon binding anticancer drug 1843U89. Nat.Struct.Biol., 2:1095-1101, 1995 Cited by PubMed Abstract: 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. PubMed: 8846221DOI: 10.1038/nsb1295-1095 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.95 Å) |
Structure validation
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