Cleavage of farnesylated COOH-terminal heptapeptide of mouse N-ras by brain microsomal membranes: evidence for a carboxypeptidase which specifically removes the COOH-terminal methionine.
Brain microsomal membranes are capable of sequentially removing Met, Leu and Val from a chemically synthesized COOH-terminal heptapeptide (propionyl-Gly-Ser-Pro-(farnesyl-Cys)-Val-Leu-Met) of mouse N-ras protein. The carboxypeptidase generating Met displays maximum activity at neutral pH and shows high affinity for the farnesylated substrate (Km = 73 microM) as compared to its non farnesylated precursor (Km = 600 microM). The results of inhibitor action suggest that the membrane carboxypeptidase is a novel, probably thiol-dependent, serine type peptidase.
Akopyan
T N
TN
Département de Chimie Organique, U266 INSERM-UA498 CNRS URA D 1500 UFR des Sciences Pharmaceutiques et Biologiques, Paris, France.
Couedel
Y
Y
Beaumont
A
A
Fournie-Zaluski
M C
MC
Roques
B P
BP
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002268:Carboxypeptidases / Q000378:metabolism*; D005204:Farnesol; D008715:Methionine / Q000378:metabolism; D051379:Mice; D008861:Microsomes / Q000378:metabolism; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D011499:Protein Processing, Post-Translational; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*
D010446:Peptide Fragments; D005204:Farnesol; D008715:Methionine; D002268:Carboxypeptidases; D016283:Proto-Oncogene Proteins p21(ras)