Leucine aminopeptidase: bestatin inhibition and a model for enzyme-catalyzed peptide hydrolysis.

摘要: The three-dimensional structures of native bovine lens leucine aminopeptidase (EC 3.4.11.1) and its complex with bestatin, a slow-binding inhibitor, have been solved exhaustively refined. mode binding bestatin to may be similar that tetrahedral intermediate is thought form during peptide bond hydrolysis. Bestatin binds in the active site alpha-amino group hydroxyl coordinated zinc ion located readily exchangeable divalent cation site. Its phenylalanyl side chain stabilized by van der Waals interactions Met-270, Thr-359, Gly-362, Ala-451, Met-454, which appear terminal hydrophobic pocket. leucyl another cleft lined Asn-330, Ala-333, Ile-421. Hydrogen bonds involving residues Lys-262, Asp-273, Gly-360, Leu-362 are responsible for stabilizing backbone nitrogen oxygen atoms bestatin. inhibition discussed correlated biochemical studies analogues. In addition, features mechanism catalysis hydrolysis discussed.