2P98
E. coli methionine aminopeptidase monometalated with inhibitor YE7
Summary for 2P98
| Entry DOI | 10.2210/pdb2p98/pdb |
| Related | 2GTX |
| Descriptor | Methionine aminopeptidase, MANGANESE (II) ION, SODIUM ION, ... (5 entities in total) |
| Functional Keywords | monometalated, mononuclear, mn(ii)-form, hydrolase, enzyme-inhibitor complex, metalloenzyme |
| Biological source | Escherichia coli |
| Total number of polymer chains | 1 |
| Total formula weight | 29414.69 |
| Authors | |
| Primary citation | Huang, M.,Xie, S.X.,Ma, Z.Q.,Huang, Q.Q.,Nan, F.J.,Ye, Q.Z. Inhibition of Monometalated Methionine Aminopeptidase: Inhibitor Discovery and Crystallographic Analysis. J.Med.Chem., 50:5735-5742, 2007 Cited by PubMed Abstract: Two divalent metal ions are commonly seen in the active-site cavity of methionine aminopeptidase, and at least one of the metal ions is directly involved in catalysis. Although ample structural and functional information is available for dimetalated enzyme, methionine aminopeptidase likely functions as a monometalated enzyme under physiological conditions. Information on structure, as well as catalysis and inhibition, of the monometalated enzyme is lacking. By improving conditions of high-throughput screening, we identified a unique inhibitor with specificity toward the monometalated enzyme. Kinetic characterization indicates a mutual exclusivity in binding between the inhibitor and the second metal ion at the active site. This is confirmed by X-ray structure, and this inhibitor coordinates with the first metal ion and occupies the space normally occupied by the second metal ion. Kinetic and structural analyses of the inhibition by this and other inhibitors provide insight in designing effective inhibitors of methionine aminopeptidase. PubMed: 17948983DOI: 10.1021/jm700930k PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.7 Å) |
Structure validation
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