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Structure of Bovine Glycine N-Acyltransferase Clarifies Its Catalytic Mechanism
Ana C Ebrecht1, Christoffel P S Badenhorst2, Uwe T Bornscheuer2
1Department of Microbiology and Biochemistry, University of the Free State, Bloemfontein 9301, South Africa.
Abstract:
Glycine N-acyltransferase (GLYAT; EC 2.3.1.13, Accession ID: AAI12537) is a key enzyme in mammalian homeostasis that has been linked to several pathologies in humans, including cancer. Here we report the first crystal structure of a member of the GLYAT family, both in the apo form as well as bound to benzoyl-CoA. Binding of glycine could be inferred from an acetate molecule from the crystallization solution. A detailed analysis of its structure and the effects of mutations of key residues helped elucidate the catalytic mechanism, showing a general base-catalyzed reaction driven by a potential low-barrier hydrogen bond (LBHB) formed between the catalytic Glu-His dyad. This work will aid further studies of GLYAT and other members of the family.
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