Structure and Function of Bovine Lens Aminopeptidase and Comparison with Homologous Aminopeptidases

Lens leucine aminopeptidase (LAP†) is the aminopeptidase for which structural, kinetic, and mechanistic information is most developed. Crystallographic, electron micrographic, NMR, and photoaffinity labeling and modeling studies indicate that lens LAP protomers are bilobal, and that bestatin and substrates are bound in an active site, which is found in the larger lobe of each protomer. Zn2+ is involved in substrate liganding and presumably in catalysis of hydrolysis. There is no evidence of an acyl-enzyme intermediate in hydrolysis. Amino acid sequences determined directly or deduced from cDNAs indicate homologies between lens aminopeptidase and APs in organisms as diverse as E. coli, particularly in catalytically important residues, or in residues involved in metal ion binding. For additional details regarding structures and function of some other APs, readers are referred to subsequent chapters in this book.