Endoproteolysis of non-CAAX-containing isoprenylated peptides.
A microsomal endoprotease specifically cleaves isoprenylated peptides of the CAAX motif, such as N-acetyl-S-all-trans-farnesyl-L-cysteine (AFC-VIM), at the isoprenylated cysteine residue. It is shown here that endoproteolysis will also occur with peptides which are not of the CAAX type. Peptide substrates modeled after the Delta virus large antigen carboxyl-terminus (CRPQ) are endoproteolytically hydrolyzed by liver microsomes. AFC-RPQ is hydrolyzed with a KM = 12.4 microM and a Vmax = 0.27 nmol/min/mg, and AGGC-RPQ is hydrolyzed with a KM = 7.9 microM and a Vmax = 0.042 nmol/min/mg. Moreover, a series of potent inhibitors of the endoproteolysis of AFC-AAX-containing peptides are ineffective at inhibiting the hydrolysis of AFC-RPQ and AGGC-RPQ, suggesting the existence of isoforms of the endoprotease.
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Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115.
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D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D010450:Endopeptidases / Q000378:metabolism*; D006868:Hydrolysis; D008862:Microsomes, Liver / Q000378:metabolism; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism*; D017368:Protein Prenylation
D009842:Oligopeptides; D010450:Endopeptidases