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Structure-function properties of prolyl oligopeptidase family enzymes

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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.

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    Dean Rea & Vilmos Fülöp

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Rea, D., Fülöp, V. Structure-function properties of prolyl oligopeptidase family enzymes. Cell Biochem Biophys 44, 349–365 (2006). https://doi.org/10.1385/CBB:44:3:349

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