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A single activity carboxyl methylates both farnesyl and geranylgeranyl cysteine residues
Author(s) -
Volker Craig,
Lane Pamela,
Kwee Cynthia,
Johnson Mark,
Stock Jeff
Publication year - 1991
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(91)81415-5
Subject(s) - cysteine , chemistry , prenylation , stereochemistry , farnesol , biochemistry , heterotrimeric g protein , farnesyl diphosphate farnesyltransferase , farnesyltransferase , enzyme , g protein , receptor
Members of the Ras superfamily of small GTP‐binding proteins, γ‐subunits of heterotrimeric G proteins and nuclear lamin B are subject to a series of post‐translational modifications that produce prenylcysteine methylester groups at their carboxyl termini. The thioether‐linked polyisoprenoid substituent can be either farnesyl (C 15 ) or geranylgeranyl (C 20 ). Small molecule prenylcysteine derivatives with either the C 15 or C 20 modification, such as N ‐acetyl‐ S‐trans,trans ‐farnesyl‐L‐cysteine (AFC), S‐trans,trans ‐farnesylthiopropionate (FTP), as well as the corresponding geranylgeranyl derivatives (AGGC and GGTP) are substrates for the carboxyl methyltransferase. Saccharomyces cerevisiae ste 14 mutants that lack RAS and a‐factor carboxyl methyltransferase activity are also unable to methylate farnesyl and geranylgeranylcysteine derivatives. Moreover, C 20 ‐substituted cysteine analogs directly compete for carboxyl methylation with the C 15 ‐substituted cysteine analogs and vice versa. Finally, AGGC is even more effective than AFC as an inhibitor of Ras carboxyl methylation, despite the fact that Ras is methylated at a farnesylcysteine rather than a geranylgeranylcysteine residue.