Crystal structures of Staphylococcusaureus methionine aminopeptidase complexed with keto heterocycle and aminoketone inhibitors reveal the formation of a tetrahedral intermediate.
Article Details
- CitationCopy to clipboard
Douangamath A, Dale GE, D'Arcy A, Almstetter M, Eckl R, Frutos-Hoener A, Henkel B, Illgen K, Nerdinger S, Schulz H, Mac Sweeney A, Thormann M, Treml A, Pierau S, Wadman S, Oefner C
Crystal structures of Staphylococcusaureus methionine aminopeptidase complexed with keto heterocycle and aminoketone inhibitors reveal the formation of a tetrahedral intermediate.
J Med Chem. 2004 Mar 11;47(6):1325-8.
- PubMed ID
- 14998322 [ View in PubMed]
- Abstract
High-resolution crystal structures of Staphylococcus aureus methionine aminopeptidase I in complex with various keto heterocycles and aminoketones were determined, and the intermolecular ligand interactions with the enzyme are reported. The compounds are effective inhibitors of the S. aureus enzyme because of the formation of an uncleavable tetrahedral intermediate upon binding. The electron densities unequivocally show the enzyme-catalyzed transition-state analogue mimicking that for amide bond hydrolysis of substrates.