title: The PREPL A protein, a new member of the prolyl oligopeptidase family, lacking catalytic activity.
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.
authors.affiliation: Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, 1518, Budapest 112, P.O. Box 7, Hungary.
authors.forename: Z
authors.initials: Z
authors.lastname: Szeltner
authors.forename: I
authors.initials: I
authors.lastname: Alshafee
authors.forename: T
authors.initials: T
authors.lastname: Juhász
authors.forename: R
authors.initials: R
authors.lastname: Parvari
authors.forename: L
authors.initials: L
authors.lastname: Polgár
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D002384:Catalysis; D004795:Enzyme Stability; D006801:Humans; D008969:Molecular Sequence Data; D000085822:Prolyl Oligopeptidases; D011487:Protein Conformation; D016415:Sequence Alignment; D012697:Serine Endopeptidases / Q000737:chemistry* / Q000145:classification / Q000378:metabolism*
chemical_list: D012697:Serine Endopeptidases; C000705287:PREPL protein, human; D000085822:Prolyl Oligopeptidases; C090703:oligopeptidase B