Insights into the Specificity of Lysine Acetyltransferases

Abstract

Background: Gcn5-related N-acetyltransferases (GNATs) modify proteins in all domains of life. Results: The structure of a GNAT was determined in complex with a protein substrate. Conclusion: Specificity of the GNAT-protein interaction is dictated by an extensive interaction surface compared with GNATpeptide structures. Significance: This is the first structure of a GNAT-protein acetylation complex, and it may enable structure-based identification and engineering of GNAT substrates.

Acylation of Biomolecules in Prokaryotes: a Widespread Strategy for the Control of Biological Function and Metabolic Stress

“…Briefly, results obtained from in vitro and in vivo analyses of single-amino-acid SePat variants showed that such variants had low enzymatic activity (70). Furthermore, results from recently reported structural work aimed at understanding the substrate specificity of Pat enzymes suggested that in the absence of the large domain of Pat, the catalytic domain of the enzyme inefficiently interacts with its protein substrate (71). Whatever the role of the N-terminal domain may be, it is likely to also play a role in sensing acetyl-CoA.…”

“…These SePat homologues are comprised of two distinct domains, a large (ϳ700-residue) N-terminal domain and the catalytic GNAT domain (ϳ200 residues) at the C terminus (68,69). Although the function of the large N-terminal domain of Pat enzymes remains largely unclear, insights into its relevance to Pat function have been reported (70,71). Briefly, results obtained from in vitro and in vivo analyses of single-amino-acid SePat variants showed that such variants had low enzymatic activity (70).…”

“…13C and D). Reversing the charges in either SeAcs CTD or SlPatA GNAT significantly decreased interactions between these proteins (71).…”

“…Recently, the first structure of a GNAT family member in complex with a protein substrate with a tertiary structure was reported (71,213). The GNAT domain from S. lividans SlPatA (SlPatA GNAT ) was crystallized in complex with the C-terminal domain of S. enterica Acs (SeAcs CTD ) (71) (Fig.…”

The Protein Acetyltransferase PatZ from Escherichia coli Is Regulated by Autoacetylation-induced Oligomerization

“…6B). In fact, it has been demonstrated that full-length SePat is necessary for efficient binding to acetyl-CoA (8) and that the specificity of the GNAT-protein interaction is dictated by an extensive interaction surface (66). Moreover, the tetramer PatZ Acs-like could not be acetylated by PatZ WT (Fig.…”