1E9F
Mutant human thymidylate kinase complexed with TMP and ADP
Summary for 1E9F
| Entry DOI | 10.2210/pdb1e9f/pdb |
| Related | 1E2D 1E2E 1E2F 1E2G 1E2Q 1E98 1E99 1E9A 1E9B 1E9C 1E9D 1E9E |
| Descriptor | THYMIDYLATE KINASE, THYMIDINE-5'-PHOSPHATE, ADENOSINE-5'-DIPHOSPHATE, ... (5 entities in total) |
| Functional Keywords | phosphotransferase, thymidylate kinase, p-loop, transferase |
| Biological source | HOMO SAPIENS More |
| Total number of polymer chains | 1 |
| Total formula weight | 25021.75 |
| Authors | Ostermann, N.,Lavie, A.,Padiyar, S.,Brundiers, R.,Veit, T.,Reinstein, J.,Goody, R.S.,Konrad, M.,Schlichting, I. (deposition date: 2000-10-11, release date: 2001-10-11, Last modification date: 2024-05-08) |
| Primary citation | Ostermann, N.,Lavie, A.,Padiyar, S.,Brundiers, R.,Veit, T.,Reintein, J.,Goody, R.S.,Konrad, M.,Schlichting, I. Potentiating Azt Activation: Structures of Wildtype and Mutant Human Thymidylate Kinase Suggest Reasons for the Mutants' Improved Kinetics with the HIV Prodrug Metabolite Aztmp J.Mol.Biol., 304:43-, 2000 Cited by PubMed Abstract: The 60-fold reduced phosphorylation rate of azidothymidine (AZT) monophosphate (AZTMP), the partially activated AZT metabolite, by human thymidylate kinase (TMPK) severely limits the efficacy of this anti-HIV prodrug. Crystal structures of different TMPK nucleotide complexes indicate that steric hindrance by the azido group of AZTMP prevents formation of the catalytically active closed conformation of the P-loop of TMPK. The F105Y mutant and a chimeric mutant that contains sequences of the human and Escherichia coli enzyme phosphorylate AZTMP 20-fold faster than the wild-type enzyme. The structural basis of the increased activity is assigned to stabilization of the closed P-loop conformation. PubMed: 11071809DOI: 10.1006/JMBI.2000.4175 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
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