Inhibition of monometalated methionine aminopeptidase: inhibitor discovery and crystallographic analysis.

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 coordinate

SUBMITTER: Huang M 

PROVIDER: S-EPMC2522305 | biostudies-literature | 2007 Nov

REPOSITORIES: biostudies-literature