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Cell Biochemistry and Biophysics

, Volume 44, Issue 3, pp 349–365 | Cite as

Structure-function properties of prolyl oligopeptidase family enzymes

  • Dean Rea
  • Vilmos FülöpEmail author
Review

Abstract

Prolyl oligopeptidase family enzymes regulate the activity of biologically active peptides and peptide hormones, and they are implicated in diseases, including amnesia, depression, diabetes, and trypanosomiasis. Distinctively, these enzymes hydrolyze only relatively short peptide substrates, while large structured peptides and proteins are not usually cleaved. Prolyl oligopeptidase has a C-terminal α/β-hydrolase catalytic domain that is similar to lipases and esterases. An N-terminal β-propeller domain regulates access to the buried active site, explaining the observed oligopeptidase activity. The catalytic and regulatory mechanisms have been investigated using a combination of X-ray crystallography, site-directed mutagenesis, and enzyme kinetic measurements. Crystal structures have now been determined for representative members of three of the four subfamilies and are facilitating a better understanding of the structure-function properties of these physiologically and pharmaceutically important enzymes.

Index Entries

Prolyl oligopeptidase oligopeptidase B dipeptidyl peptidase IV acylaminoacyl peptidase serine peptidase catalytic triad 

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Copyright information

© Humana Press Inc. 2006

Authors and Affiliations

  1. 1.Department of Biological SciencesUniversity of WarwickCoventryUK

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