Mimic Aids Study Of Protein Acetylation

Like protein phosphorylation, acetylation of lysine residues on proteins may have an important regulatory role in cell pathways. Thousands of mammalian proteins are naturally acetylated, but it’s technically difficult to acetylate lysine groups in the lab, complicating the study of the functional consequences of acetylation. Philip A. Cole of Johns Hopkins University School of Medicine and coworkers have now developed an easier method: derivatizing cysteines with methylthiocarbonyl-aziridine (MTCA) to create a thiocarbamate mimic of acetyl-lysine groups (J. Am. Chem. Soc., DOI: 10.1021/ja103954u). This modification is recognized by acetyl-lysine-specific antibodies and by the Brdt bromodomain, a protein receptor that binds acetylated lysines, suggesting that MTCA-modified cysteine is a good stand-in for acetyl-lysine. Unlike acetyl-lysine, the thiocarbamate mimic can’t be deacetylated enzymatically, a property that could make it easier to determine function in deacetylase-rich cell environments. Cole and coworkers demonstrated the utility of the mimic by using it to activate a histone acetyltransferase and a protein kinase, enzymes that are believed to regulate a wide range of cellular processes. The simple method “could be quite useful in biochemistry,” Cole believes.