Cellular and Molecular Life Sciences CMLS

, Volume 62, Issue 19, pp 2376–2381

The PREPL A protein, a new member of the prolyl oligopeptidase family, lacking catalytic activity

  • Z. Szeltner
  • I. Alshafee
  • T. Juhász
  • R. Parvari
  • L. Polgár
Research Article

DOI: 10.1007/s00018-005-5262-5

Cite this article as:
Szeltner, Z., Alshafee, I., Juhász, T. et al. Cell. Mol. Life Sci. (2005) 62: 2376. doi:10.1007/s00018-005-5262-5

Abstract.

The PREPL (previously called KIAA0436) gene encodes a putative serine peptidase from the prolyl oligopeptidase family. A chromosomal deletion involving the PREPL gene leads to a severe syndrome with multiple symptoms. Homology with oligopeptidase B suggested that the enzyme cleaves after an arginine or lysine residue. Several PREPL splice variants have been identified, and a 638-residue variant (PREPL A) was expressed in Escherichia coli and purified. Its secondary structure was similar to that of oligopeptidase B, but differential-scanning calorimetry indicated a higher conformational stability. Dimerization may account for the enhanced stability. 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. These results indicated that the catalytic serine is a reactive residue. However, the negligible hydrolytic activity suggests that the function of PREPL A is different from that of the other members of the prolyl oligopeptidase family.

Key words.

KIAA0436oligopeptidase Bprotein expression and isolationhydrolytic activitydimerizationdenaturation

Copyright information

© Birkhäuser Verlag, Basel 2005

Authors and Affiliations

  • Z. Szeltner
    • 1
  • I. Alshafee
    • 2
  • T. Juhász
    • 1
  • R. Parvari
    • 2
  • L. Polgár
    • 1
  1. 1.Institute of Enzymology, Biological Research CenterHungarian Academy of SciencesBudapest 112Hungary
  2. 2.Department of Developmental Molecular Genetics, Faculty of Health SciencesBen Gurion University of the NegevBeer ShevaIsrael