Crystal structure of an acylpeptide hydrolase/esterase from Aeropyrum pernix K1

Structure. 2004 Aug;12(8):1481-8. doi: 10.1016/j.str.2004.05.019.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aeropyrum / enzymology
  • Amino Acids / chemistry
  • Crystallography, X-Ray
  • Esterases / chemistry*
  • Models, Molecular*
  • Nitrophenols / chemistry*
  • Organophosphorus Compounds / chemistry*
  • Peptide Hydrolases / chemistry*
  • Peptides / chemistry*
  • Protein Structure, Tertiary

Substances

  • Amino Acids
  • Nitrophenols
  • Organophosphorus Compounds
  • Peptides
  • nitrophenylphosphate
  • Esterases
  • Peptide Hydrolases
  • acylaminoacyl-peptidase

Associated data

  • PDB/1VE6
  • PDB/1VE7