Purification and characterization of pig kidney aminopeptidase P. A glycosyl-phosphatidylinositol-anchored ectoenzyme

Biochem J. 1990 Apr 15;267(2):509-15. doi: 10.1042/bj2670509.

Abstract

Aminopeptidase P (EC 3.4.11.9) was solubilized from pig kidney membranes with bacterial phosphatidylinositol-specific phospholipase C (PI-PLC) and then purified by a combination of anion-exchange and hydrophobic-interaction chromatographies. Contaminating peptidase activities were removed by selective affinity chromatography. The purified enzyme was apparently homogeneous on SDS/PAGE with an Mr of 91,000. Enzymic deglycosylation revealed that aminopeptidase P is a glycoprotein, with up to 25% by weight of the protein being due to the presence of N-linked sugars. The phospholipase-solubilized aminopeptidase P was recognized by an antiserum to the cross-reacting determinant (CRD) characteristic of the glycosyl-phosphatidylinositol anchor. This recognition was abolished by mild acid treatment or deamination with HNO2, indicating that the CRD was due exclusively to the inositol 1,2-cyclic phosphate ring epitope generated by the action of PI-PLC. The activity of aminopeptidase P was inhibited by chelating agents and was stimulated by Mn2+ or Co2+ ions, confirming the metallo-enzyme nature of this peptidase. Selective inhibitors of other aminopeptidases (actinonin, amastatin, bestatin and puromycin) had little or no inhibitory effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminopeptidases / antagonists & inhibitors
  • Aminopeptidases / isolation & purification*
  • Aminopeptidases / metabolism
  • Animals
  • Cations, Divalent
  • Cell Membrane / enzymology
  • Chromatography, Affinity
  • Chromatography, Gel
  • Chromatography, Ion Exchange
  • Electrophoresis, Polyacrylamide Gel
  • Glycolipids / metabolism*
  • Glycosylphosphatidylinositols
  • Kidney / enzymology*
  • Kinetics
  • Phosphatidylinositols / metabolism*
  • Protease Inhibitors / pharmacology
  • Solubility
  • Swine

Substances

  • Cations, Divalent
  • Glycolipids
  • Glycosylphosphatidylinositols
  • Phosphatidylinositols
  • Protease Inhibitors
  • Aminopeptidases
  • X-Pro aminopeptidase