| Structural highlights
3pke is a 1 chain structure with sequence from "bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , |
| Related: | 3iu7, 3iu8, 3iu9, 3pka, 3pkb, 3pkc, 3pkd |
| Gene: | map, mapB, MT2929, MTV003.07c, Rv2861c ("Bacillus tuberculosis" (Zopf 1883) Klein 1884) |
| Activity: | Methionyl aminopeptidase, with EC number 3.4.11.18 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[AMPM2_MYCTU] Removes the N-terminal methionine from nascent proteins, when the penultimate amino acid is alanine or proline, but enzyme activity is remarkably low when the second residue is phenylalanine or leucine. With glycine at the second position, Map is more active with a tetrapeptide than with a tripeptide.[1] [2]
Publication Abstract from PubMed
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.
Inhibition of Mycobacterium tuberculosis Methionine Aminopeptidases by Bengamide Derivatives.,Lu JP, Yuan XH, Yuan H, Wang WL, Wan B, Franzblau SG, Ye QZ ChemMedChem. 2011 Apr 4. doi: 10.1002/cmdc.201100003. PMID:21465667[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Zhang X, Chen S, Hu Z, Zhang L, Wang H. Expression and characterization of two functional methionine aminopeptidases from Mycobacterium tuberculosis H37Rv. Curr Microbiol. 2009 Nov;59(5):520-5. doi: 10.1007/s00284-009-9470-3. Epub 2009, Aug 18. PMID:19688379 doi:10.1007/s00284-009-9470-3
- ↑ Lu JP, Chai SC, Ye QZ. Catalysis and Inhibition of Mycobacterium tuberculosis Methionine Aminopeptidase. J Med Chem. 2009 Dec 28. PMID:20038112 doi:10.1021/jm901624n
- ↑ Lu JP, Yuan XH, Yuan H, Wang WL, Wan B, Franzblau SG, Ye QZ. Inhibition of Mycobacterium tuberculosis Methionine Aminopeptidases by Bengamide Derivatives. ChemMedChem. 2011 Apr 4. doi: 10.1002/cmdc.201100003. PMID:21465667 doi:10.1002/cmdc.201100003
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