Identifying the recognition unit for G protein methylation

• Published in: The Journal of biological chemistry Vol. 266; no. 17; pp. 10719 - 10722
• Main Authors: ENG WUI TAN, PEREZ-SALA, D, CANADA, F. J, RANDO, R. R
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Biochemistry and Molecular Biology 15.06.1991
• Subjects: Analytical, structural and metabolic biochemistry; Animals; Biological and medical sciences; Cattle; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; GTP-Binding Proteins - metabolism; Kinetics; Macromolecular Substances; Magnetic Resonance Spectroscopy; Methylation; Methyltransferases - metabolism; Molecular Structure; Rod Cell Outer Segment - metabolism; S-Adenosylmethionine - analogs & derivatives; S-Adenosylmethionine - chemical synthesis; S-Adenosylmethionine - metabolism; Substrate Specificity; Transducin - metabolism; Transferases; Site specificity; Vertebrata; Mammalia; Bovine; Radiolabelling; Enzyme; Substrate specificity; Methyltransferase; Transducin; Artiodactyla; Ungulata; G protein
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(18)99074-5

Signal transducing G proteins, such as transducin, are prenylated and methylated at carboxyl-terminal cysteine residues. The methylation of transducin occurs by means of a membrane bound S-adenosyl methionine-dependent methyltransferase. This methyltransferase accepts the simple modified amino acid N-acetyl-S-farnesyl-L-cysteine (AFC) as a substrate. This means that the enzyme does not require peptide sequences of transducin in a putative substrate. Moreover, small structural changes in the AFC structural unit all lead to molecules incapable of being substrates. For example, neither N-acetyl-S-farnesylhomocysteine (AFHC) nor the saturated form of AFC are substrates. Interestingly, substitution of the N-acetyl moiety of AFC with a hydrogen atom leads to S-farnesylthiopropionic acid (FTP), which is an excellent substrate for the methyltransferase. The methyltransferase shows great specificity for the the FTP pharmacophore. So far, alterations in this structure have not led to active substrates. For example, removal of a methylene group of FTP, producing S-farnesylthioacetic acid (FTA), abolished substrate activity. FTA is a potent competitive inhibitor of the enzyme. FTP is thus the ultimately simplified substrate for the methyltransferase and does not contain any remnants of the peptide structure of transducin.