Endoproteolysis of non‐CAAX‐containing isoprenylated peptides

FEBS Letters

Rando, Robert R.¹  Ma, Yu-Ting¹ 

[1] Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA

关键词: Endoproteolysis;    Isoprenylated peptide;    Inhibitor;    DMSO;    dimethylsulfoxide;    AFC;    TV-acetyl-S-all-ttms-farnesyl-l-cysteine;    AGGC;    N-acetyl-S-all-trans-geranylgeranyl-l-cysteine;    BFC;    N-t-Boc-all-mwu-farnesyl-l-cysteine;    DMF;    dimethyl-formamide;    DMAP;    4;    4-(dimethylamino)pyridine;    PNB;    p-nitroben-zyl;    Arg;    arginine;    Pro;    proline;    Gln;    glutamine;   

DOI  :  10.1016/0014-5793(93)80493-E

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 K _M = 12.4 μM and a V _max= 0.27 nmolmin/mg, and AGGC-RPQ is hydrolyzed with a K _M= 7.9 μM and a V _max = 0.042 nmolmin/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.

【 授权许可】

Unknown