Acylpeptide hydrolases (APH; also known as acylamino acid releasing enzyme) catalyze the removal of an N-acylated amino acid from blocked peptides. The crystal structure of an APH from the thermophilic archaeon Aeropyrum pernix K1 to 2.1 A resolution confirms it to be a member of the prolyl oligopeptidase family of serine proteases. The structure of apAPH is a symmetric homodimer with each subunit comprised of two domains. The N-terminal domain is a regular seven-bladed beta-propeller, while the C-terminal domain has a canonical alpha/beta hydrolase fold and includes the active site and a conserved Ser445-Asp524-His556 catalytic triad. The complex structure of apAPH with an organophosphorus substrate, p-nitrophenyl phosphate, has also been determined. The complex structure unambiguously maps out the substrate binding pocket and provides a basis for substrate recognition by apAPH. A conserved mechanism for protein degradation from archaea to mammals is suggested by the structural features of apAPH.
Bartlam M, Wang G, Yang H, Gao R, Zhao X, Xie G, Cao S, Feng Y, Rao Z (2004) Crystal Structure of an Acylpeptide Hydrolase/Esterase from Aeropyrum pernix K1. Structure(Camb)12: 1481-8
Bartlam M, Wang G, Yang H, Gao R, Zhao X, Xie G, Cao S, Feng Y, Rao Z (2004) Structure(Camb)12: 1481-8
