Prolyl endopeptidase catalysis. A physical rather than a chemical step is rate-limiting.

  title={Prolyl endopeptidase catalysis. A physical rather than a chemical step is rate-limiting.},
  author={László Polgár},
  journal={The Biochemical journal},
  volume={283 ( Pt 3)},
  • L. Polgár
  • Published 1992
  • Chemistry, Medicine
  • The Biochemical journal
Prolyl endopeptidase represents a new family of serine proteases, and it has a mechanistic feature distinct from that of the enzymes of the extensively studied chymotrypsin and subtilisin families. The rate-determining step in the catalysis of serine proteases is a general base/acid-catalysed chemical step. For prolyl endopeptidase, however, the chemical step is not rate-limiting, as demonstrated by using substrates with different leaving groups. It is known that the acylation of chymotrypsin… Expand
Unusual secondary specificity of prolyl oligopeptidase and the different reactivities of its two forms toward charged substrates.
A negatively charged active site exists at high pH and exerts electrostatic attraction or repulsion toward charged substrates, which suggests that the enzyme binds its substrate in a special manner. Expand
Characterization of a novel acylaminoacyl peptidase with hexameric structure and endopeptidase activity.
It was shown that PhAAP is not just an acylaminoacyl peptidase, but it also has an endopeptidase activity and so differs from the mammalian AAPs and suggests that its cellular function may be different from that of the dimeric AAP also found in the same organism. Expand
Substrate-dependent Competency of the Catalytic Triad of Prolyl Oligopeptidase*
The catalytic competence of the Asp641 residue of the catalytic triad was studied using the D641N and D641A variants of the enzyme, and Crystal structure determination of these mutants revealed subtle perturbations related to the catalyst activity. Expand
[14] Prolyl oligopeptidases
Publisher Summary This chapter focuses on prolyl oligopeptidases. This enzyme degrades a variety of proline-containing peptides by cleaving the peptide bond at the carboxy side of proline residues.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
Structure and Catalysis of Acylaminoacyl Peptidase
The structure and the kinetics of two mutant enzymes in which the aspartic acid of the catalytic triad was changed to alanine or asparagine are investigated and it is concluded that the two forms are at equilibrium and the substrates bind by the conformational selection mechanism. Expand
Cleavage of the Lys196-Ser197 bond of prolyl oligopeptidase: enhanced catalytic activity for one of the two active enzyme forms.
The digestion experiments suggested that alteration in the ionic strength elicits conformational changes in native prolyl oligopeptidase, and this may account for the enhanced catalytic activity observed at higher ionsic strength. Expand
Review The prolyl oligopeptidase family
The recent crystal structure deter- mination of prolyl oligopeptidase has shown that the enzyme contains a peptidase domain with an a/b hydrolase fold, and its catalytic triad is covered by the central tunnel of an unusual seven-bladed b-propeller. Expand
Kinetic Landscape of a Peptide Bond-Forming Prolyl Oligopeptidase
This is the first detailed description of the kinetic sequence of a macrocyclase enzyme from this class, and this work is a necessary step toward designing broad-specificity efficient macrocyclases. Expand
Prolyl oligopeptidase catalysis Reactions with thiono substrates reveal substrate‐induced conformational change to be the rate‐limiting step
A kinetic study using the thiono substrate, benzyloxycarbonyl‐Gly‐Pro[CS‐NH]‐2‐naphthylamide, suggests that the putative oxyanion binding site is important in prolyl oligopeptidase catalysis, although to a lesser extent than in the chymotrypsin‐and subtilisin‐catalyzed reactions. Expand