Acetylation and deacetylation reactions result in biologically important modifications that are involved in normal cell function and
cancer development. These reactions, carried out by
protein acetyltransferase enzymes, act by transferring an acetyl group from acetyl-coenzymeA (Ac-
CoA) to various substrate
proteins. Such
protein acetylation remains poorly understood in Archaea, and has been only partially described. Information processing in Archaea has been reported to be similar to that in eukaryotes and distinct from the equivalent bacterial processes. The human N-
acetyltransferase Ard1 (hArd1) is one of the
acetyltransferases that has been found to be overexpressed in various
cancer cells and tissues, and knockout of the hArd1 gene significantly reduces growth rate of the
cancer cell lines. In the present study, we determined the crystal structure of Thermoplasma volcanium Ard1 (Tv Ard1), which shows both
ligand-free and multiple
ligand-bound forms, i.e.,Ac-
CoA- and coenzyme A (
CoA)-bound forms. The difference between
ligand-free and
ligand-bound chains in the crystal structure was used to search for the interacting residues. The re-orientation and position of the loop between β4 and α3 including the
phosphate-binding loop (P-loop) were observed, which are important for the
ligand interaction. In addition, a biochemical assay to determine the N-
acetyltransferase activity of Tv Ard1 was performed using the T.volcanium substrate
protein Alba (Tv Alba). Taken together, the findings of this study elucidate
ligand-free form of Tv Ard1 for the first time and suggest multiple modes of binding with Ac-
CoA and CoA.