Acetyl-group sensing through modulation of conformational dynamics in an
arylalkylamine N-acetyltransferase.

Adam A Aboalroub, and Ioannis Gelis

University of South Florida

The transfer of an acetyl group from Ac-CoA to an acceptor amine is catalyzed by Gcn5-related N-acetyltransferases (GNATs). Despite the agreement that this acetylation process proceeds through an ordered sequential mechanism, the role of the acetyl group in driving this mechanism remains elusive.
Using NMR spectroscopy, ITC, and kinetic experiment, we show that the position of the acetyl group during catalysis regulates protein conformational dynamics. Part of the substrate binding site switches from a stable-ordered state in the presence of acetyl-CoA to a conformational labile ensemble of structures in the presence of CoA which may allow for the ordered binding of substrates and release of products.