4pv6
Crystal Structure Analysis of Ard1 from Thermoplasma volcanium
Structural highlights
FunctionPublication Abstract from PubMedAcetylation 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 beta4 and alpha3 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. Structure of Thermoplasma volcanium Ard1 belongs to N-acetyltransferase family member suggesting multiple ligand binding modes with acetyl coenzyme A and coenzyme A.,Ma C, Pathak C, Jang S, Lee SJ, Nam M, Kim SJ, Im H, Lee BJ Biochim Biophys Acta. 2014 Oct;1844(10):1790-7. doi:, 10.1016/j.bbapap.2014.07.011. Epub 2014 Jul 22. PMID:25062911[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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