Crystal Structures of Staphylococcusaureus Methionine AminopeptidaseComplexed with Keto Heterocycle andAminoketone Inhibitors Reveal theFormation of a Tetrahedral Intermediate
High-resolution crystal structures of Staphylococcusaureus methionine aminopeptidase I in complex withvarious keto heterocycles and aminoketones were determined,and the intermolecular ligand interactions with the enzymeare reported. The compounds are effective inhibitors of the S.aureus enzyme because of the formation of an uncleavabletetrahedral intermediate upon binding. The electron densitiesunequivocally show the enzyme-catalyzed transition-stateanalogue mimicking that for amide bond hydrolysis of substrates.
