Slipping In An Acetyl For Enzyme Control

Acetylation of proteins helps biological cells control a number of processes, including glycolysis and DNA repair. But the inability to install an acetyl group on a specific lysine residue in the lab has stymied biochemical studies of this posttranslational modification. A team led by Leo C. James and Jason W. Chin of the Medical Research Council Laboratory of Molecular Biology, in Cambridge, England, has used a method previously created by Chin’s group to help rectify this problem. The researchers produced cyclophilin A (CypA) proteins in Escherichia coli that have acetyl groups installed at a targeted lysine residue (Nat. Chem. Biol., DOI: 10.1038/nchembio.342). They found that this particular acetylation, located in the active site of CypA, blocks the enzyme’s ability to perform cis-trans isomerization of peptide bonds next to proline residues. CypA is thought to help HIV-1 infection by isomerizing the viral capsid and triggering disassembly, James notes. Because acetylation inhibits CypA cis-trans catalysis, the team predicts it would inhibit disassembly and hinder infection and could one day be the focus of antiviral treatments.