Corpus ID: 45710682

Prolyl oligopeptidase: an unusual beta-propeller domain regulates proteolysis.

  title={Prolyl oligopeptidase: an unusual beta-propeller domain regulates proteolysis.},
  author={V. F{\"u}l{\"o}p and Z. B{\"o}cskei and L. Polgár},
  volume={94 2},
Prolyl oligopeptidase is a large cytosolic enzyme that belongs to a new class of serine peptidases. The enzyme is involved in the maturation and degradation of peptide hormones and neuropeptides, which relate to the induction of amnesia. The 1.4 A resolution crystal structure is presented here. The enzyme contains a peptidase domain with an alpha/beta hydrolase fold, and its catalytic triad (Ser554, His680, Asp641) is covered by the central tunnel of an unusual beta propeller. This domain makes… Expand
Truncated prolyl oligopeptidase from Pyrococcus furiosus
It was concluded that the N‐terminal segment did not facilitate the substrate binding, independent of the size of the substrate, but contributed principally to the protein stability required for the formation of the proper active site. Expand
Prolyl endopeptidases
The structure and function of prolyl endopeptidase (PEP) enzymes and how they are being evaluated as drug targets and therapeutic agents are described. Expand
The PREPL A protein, a new member of the prolyl oligopeptidase family, lacking catalytic activity
Unexpectedly, the PREPL A protein did not cleave peptide substrates containing a P1 basic residue, but did slowly hydrolyse an activated ester substrate, and reacted with diisopropyl fluorophosphate, suggesting that the catalytic serine is a reactive residue. Expand
Mycobacterium tuberculosis puromycin hydrolase displays a prolyl oligopeptidase fold and an acyl aminopeptidase activity
The crystal structure of a M. tuberculosis puromycin hydrolase peptidase has been determined at 3 Angstrom resolution, revealing a conserved prolyl oligopeptidase fold defined by α/β‐hydrolase and β‐propeller domains with two distinctive loops that occlude access of large substrates to the active site. Expand
Carboxypeptidase in prolyl oligopeptidase family: Unique enzyme activation and substrate-screening mechanisms
This work has identified a new type within POP enzymes that exhibits not only unique activity but also a novel substrate-screening mechanism. Expand
Crystal structure of an acylpeptide hydrolase/esterase from Aeropyrum pernix K1.
The crystal structure of an APH from the thermophilic archaeon Aeropyrum pernix K1 to 2 confirms it to be a member of the prolyl oligopeptidase family of serine proteases and suggests a conserved mechanism for protein degradation from archaea to mammals. Expand
Understanding the cellular role of prolyl oligopeptidase
It has been determined that DpoA is highly similar to the mammalian enzyme and it has been demonstrated that while some variation was observed at the sequence level there is clear homology around the active site and the catalytic triad is conserved. Expand
Crystal Structures of Trypanosoma brucei Oligopeptidase B Broaden the Paradigm of Catalytic Regulation in Prolyl Oligopeptidase Family Enzymes
These ligand-free open state and inhibitor-bound closed state crystal structures of oligopeptidase B from Trypanosoma brucei, the causative agent of African sleeping sickness, are presented and show the importance of structural dynamics, governed by a fine enthalpic and entropic balance, in substrate size selectivity and catalysis. Expand
Mechanisms of Intramolecular Communication in a Hyperthermophilic Acylaminoacyl Peptidase: A Molecular Dynamics Investigation
The investigation shows that the N-terminal α1-helix mediates structural intramolecular communication to the catalytic site, concurring to the maintenance of a proper functional architecture of the catalysttic triad. Expand
The catalytic triad of serine peptidases
  • L. Polgár
  • Biology, Medicine
  • Cellular and Molecular Life Sciences CMLS
  • 2005
Several new families have been discovered, in which the nucleophile-base-acid pattern is generally conserved, but the individual components can vary, illustrating how different groups and different protein structures achieve the same reaction. Expand