Mutational analysis of the integral membrane methyltransferase isoprenylcysteine carboxyl methyltransferase (ICMT) reveals potential substrate binding sites.

ABSTRACT: The eukaryotic integral membrane enzyme isoprenylcysteine carboxyl methyltransferase (ICMT) methylates the carboxylate of a lipid-modified cysteine at the C terminus of its protein substrates. This is the final post-translational modification of proteins containing a CAAX motif, including the oncoprotein Ras, and therefore, ICMT may serve as a therapeutic target in cancer development. ICMT has no discernible sequence homology with soluble methyltransferases, and aspects of its catalytic mechanism are unknown. For example, how both the methyl donor S-adenosyl-l-methionine (AdoMet), which is water-soluble, and the methyl acceptor isoprenylcysteine, which is lipophilic, are recognized within the same active site is not clear. To identify regions of ICMT critical for activity, we combined scan

SUBMITTER: Diver MM 

PROVIDER: S-EPMC4176209 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature