D. M. Grant Pages 465 - 470 ( 6 )
A large body of biochemical, kinetic and molecular information, accumulated over the course of more than 80 years, has produced valuable insights into the relationship between the structures and the catalytic functions of the human arylamine Nacetyltransferases NAT1 and NAT2. Much of the groundwork for the determination of human NAT structures and functions was provided by seminal biochemical and enzyme kinetic studies in both human and non-human model systems, the cloning and primary amino acid sequence determination of eukaryotic and prokaryotic NATs, the characterization of naturally occurring and artificially mutated forms of human NATs, elucidation of the crystal structures of several prokaryotic NAT orthologues, and information that has been derived from cross-species comparisons. In 2007 the progress of these studies was aided substantially by the successful crystallization and direct structural analysis of human NAT1 and NAT2. The purpose of this review is to give a brief historical perspective, to summarize our current understanding of human NAT structures and functions based on both earlier and more recent work, and to provide some future insights into the potential applications of this information to the prediction of therapeutic and toxic outcomes associated with the acetylation of primary aromatic amine- and hydrazine-containing chemicals.
Human arylamine N-acetyltransferases, NAT1, NAT2, crystal structures, structure-function studies, allelic variants
Department of Pharmacology and Toxicology, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada.