Crystal structure of an acylpeptide hydrolase/esterase from Aeropyrum pernix K1.
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
Mark
M
Laboratory of Structural Biology, Tsinghua University and National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, Beijing 100084, China.
Wang
Ganggang
G
Yang
Haitao
H
Gao
Renjun
R
Zhao
Xiaodong
X
Xie
Guiqiu
G
Cao
Shuigui
S
Feng
Yan
Y
Rao
Zihe
Z
D041522:Aeropyrum / Q000201:enzymology; D000596:Amino Acids / Q000737:chemistry; D018360:Crystallography, X-Ray; D004950:Esterases / Q000737:chemistry*; D008958:Models, Molecular; D009596:Nitrophenols / Q000737:chemistry*; D009943:Organophosphorus Compounds / Q000737:chemistry*; D010447:Peptide Hydrolases / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D017434:Protein Structure, Tertiary
D000596:Amino Acids; D009596:Nitrophenols; D009943:Organophosphorus Compounds; D010455:Peptides; C008644:nitrophenylphosphate; D004950:Esterases; D010447:Peptide Hydrolases; C038220:acylaminoacyl-peptidase