3PKE
M. tuberculosis MetAP with bengamide analog Y10, in Ni form
Summary for 3PKE
Entry DOI | 10.2210/pdb3pke/pdb |
Related | 3IU7 3IU8 3IU9 3PKA 3PKB 3PKC 3PKD |
Descriptor | Methionine aminopeptidase, (E,2R,3R,4S,5R)-N-(2,3-dihydro-1H-inden-2-yl)-2-methoxy-8,8-dimethyl-3,4,5-tris(oxidanyl)non-6-enamide, NICKEL (II) ION, ... (6 entities in total) |
Functional Keywords | hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
Biological source | Mycobacterium tuberculosis |
Total number of polymer chains | 1 |
Total formula weight | 31548.28 |
Authors | |
Primary citation | Lu, J.P.,Yuan, X.H.,Yuan, H.,Wang, W.L.,Wan, B.,Franzblau, S.G.,Ye, Q.Z. Inhibition of Mycobacterium tuberculosis Methionine Aminopeptidases by Bengamide Derivatives. Chemmedchem, 6:1041-1048, 2011 Cited by PubMed Abstract: Methionine aminopeptidase (MetAP) carries out an essential function of protein N-terminal processing in many bacteria and is a promising target for the development of novel antitubercular agents. Natural bengamides potently inhibit the proliferation of mammalian cells by targeting MetAP enzymes, and the X-ray crystal structure of human type 2 MetAP in complex with a bengamide derivative reveals the key interactions at the active site. By preserving the interactions with the conserved residues inside the binding pocket while exploring the differences between bacterial and human MetAPs around the binding pocket, seven bengamide derivatives were synthesized and evaluated for inhibition of MtMetAP1a and MtMetAP1c in different metalloforms, inhibition of M. tuberculosis growth in replicating and non-replicating states, and inhibition of human K562 cell growth. Potent inhibition of MtMetAP1a and MtMetAP1c and modest growth inhibition of M. tuberculosis were observed for some of these derivatives. Crystal structures of MtMetAP1c in complex with two of the derivatives provided valuable structural information for improvement of these inhibitors for potency and selectivity. PubMed: 21465667DOI: 10.1002/cmdc.201100003 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (1.6 Å) |
Structure validation
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