2q93
E. coli methionine aminopeptidase Mn-form with inhibitor B21
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OverviewOverview
ABSTRACT: BACKGROUND: Methionine aminopeptidase is a potential target of, future antibacterial and anticancer drugs. Structural analysis of, complexes of the enzyme with its inhibitors provides valuable information, for structure-based drug design efforts. RESULTS: Five new X-ray, structures of such enzyme-inhibitor complexes were obtained. Analysis of, these and other three similar structures reveals the adaptability of a, surface-exposed loop bearing Y62, H63, G64 and Y65 (the YHGY loop) that is, an integral part of the substrate and inhibitor binding pocket. This, adaptability is important for accommodating inhibitors with variations in, size. When compared with the human isozymes, this loop either becomes, buried in the human type I enzyme due to an N-terminal extension that, covers its position or is replaced by a unique insert in the human type II, enzyme. CONCLUSIONS: The adaptability of the YHGY loop in E. coli, methionine aminopeptidase, and likely in other bacterial methionine, aminopeptidases, enables the enzyme active pocket to accommodate, inhibitors of differing size. The differences in this adaptable loop, between the bacterial and human methionine aminopeptidases is a structural, feature that can be exploited to design inhibitors of bacterial methionine, aminopeptidases as therapeutic agents with minimal inhibition of the, corresponding human enzymes.
About this StructureAbout this Structure
2Q93 is a Single protein structure of sequence from Escherichia coli with , and as ligands. Active as Methionyl aminopeptidase, with EC number 3.4.11.18 Full crystallographic information is available from OCA.
ReferenceReference
Structural analysis of inhibition of E. coli methionine aminopeptidase: implication of loop flexibility in selective inhibition of bacterial enzymes., Ma ZQ, Xie SX, Huang QQ, Nan FJ, Hurley TD, Ye QZ, BMC Struct Biol. 2007 Dec 19;7(1):84. PMID:18093325
Page seeded by OCA on Wed Jan 23 11:19:40 2008