title: Substrate specificity of the isoprenylated protein endoprotease.
abstract: Proteins containing a CAAX motif at their carboxyl termini are subject to isoprenylation at the cysteine residue. Proteolytic trimming of isoprenylated proteins is essential in the activation of these proteins. A microsomal endopeptidase activity has been identified which cleaves all-trans farnesylated cysteine containing tetrapeptides between the modified residue and the adjacent amino acid to liberate the modified cysteine residue and an intact tripeptide. Structure/activity studies are reported here on this endopeptidase activity which are consistent with the premise that this protease is identical to the one normally involved in the cellular isoprenylation pathway. The protease only processes peptides which possess an isoprenyl moiety. Within the isoprenyl series, the enzyme hydrolyzes all-trans-farnesyl-, all-trans-geranylgeranyl-, and geranyl-containing peptides. The protease also recognizes the AAX sequence, because the protease behaves either stereospecifically or stereoselectively with respect to the individual amino acids of the tripeptide. The enzyme only measurably hydrolyzes isoprenylated peptides possessing L-amino acids at C and A. On the other hand, there is a small but measurable hydrolysis of isoprenylated peptides containing a D-amino acid at X.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Y T
authors.initials: YT
authors.lastname: Ma
authors.forename: A
authors.initials: A
authors.lastname: Chaudhuri
authors.forename: R R
authors.initials: RR
authors.lastname: Rando
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D010450:Endopeptidases / Q000378:metabolism*; D008862:Microsomes, Liver / Q000201:enzymology; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*; D017368:Protein Prenylation; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D009842:Oligopeptides; D010450:Endopeptidases