title: Human-liver alanine aminopeptidase. A kinin-converting enzyme sensitive to beta-lactam antibiotics.
abstract: Human liver alanine aminopeptidase (EC 3.4.11.14; L-alpha-aminoacyl-peptide hydrolase) catalyzes the stepwise hydrolysis of methionyl-lysyl-bradykinin to yield methionine, lysine, and the limit nonapeptide, bradykinin which is resistant to further hydrolytic cleavage by this enzyme. Alanine aminopeptidase also catalyzes the hydrolysis of various neutral amino acid beta-naphthylamides. This enzyme cleaves N-terminal arginyl residues unless the adjacent penultimate residue is proline as is the case for bradykinin. The properties are consistent with the requirements of a kinin converting enzyme. Human alanine aminopeptidase activity is reduced by several beta-lactam antibiotics, with the cloxacillin, oxacillin, and methicillin Ki values being 0.51 mM, 1.6 mM, and 2.4 mM respectively. Our experiments with radioactively labelled penicillin indicate that two moles of antibiotic are bound per mole of enzyme. Neither chromatography of the penicillin-treated enzyme on G-25 Sephadex, treatment of penicillin-G-treated enzyme with penicillinase, nor extensive dilution of cloxacillin-treated enzyme diminished the degree of inactivation produced. Inhibition was obtained with 6-aminopenicillanic acid, which indicated that the penicillin nucleus itself was being bound, but substitutions, as in cloxacillin, could enhance the binding.
mesh_terms: D000626:Aminopeptidases / Q000302:isolation & purification / Q000378:metabolism*; D018826:CD13 Antigens; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008715:Methionine / Q000031:analogs & derivatives / Q000494:pharmacology; D010400:Penicillin G / Q000494:pharmacology; D010406:Penicillins / Q000494:pharmacology*; D011485:Protein Binding; D013329:Structure-Activity Relationship
chemical_list: D010406:Penicillins; D008715:Methionine; D000626:Aminopeptidases; D018826:CD13 Antigens; D010400:Penicillin G; C018594:methioninamide