title: Crystal structure of arylamine N-acetyltransferases: insights into the mechanisms of action and substrate selectivity.
abstract: BACKGROUND
  Arylamine N-acetyltransferases (NATs) are polymorphic xenobiotic metabolizing enzymes catalyzing the acetylation of aromatic amine chemicals of pharmacological/toxicological relevance (drugs, carcinogens). NATs are primordial determinants of the detoxification and/or bioactivation of these compounds. These enzymes are found in prokaryotes and eukaryotes. Several NAT isoenzymes may be present in one organism, and their substrate specificity profile and pattern of tissue expression suggest distinct functional roles.
  
  
  METHODS
  Many advances in NAT mechanism, substrate specificity, and functional impact of polymorphism have come from crystallographic and NMR studies. To date, the crystal structures of 10 different NAT homologues have been solved, including two human isoforms and several bacterial NATs. The authors present the most recent snapshot in NAT structure differences and similarities. The authors also depict the structural bases of substrate/inhibitor recognition and specificity, cofactor binding, catalytic mechanism, genetic regulation (polymorphism), and enzyme inhibition.
  
  
  CONCLUSIONS
  The determination of other NATs structures will help to develop specific inhibitors of NAT enzymes with potential clinical relevance. In addition, it will contribute to the identification of endogenous substrates and novel functions associated to this family of enzymes.
authors.affiliation: Univ Paris Diderot, Sorbonne Paris Cité, Unité de Biologie Fonctionnelle et Adaptative, CNRS EAC4413, 75013, Paris, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Kubiak
authors.forename: Julien
authors.initials: J
authors.lastname: Dairou
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Dupret
authors.forename: Fernando
authors.initials: F
authors.lastname: Rodrigues-Lima
mesh_terms: D000107:Acetylation; D001191:Arylamine N-Acetyltransferase / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics*; D001419:Bacteria / Q000201:enzymology; D001711:Biotransformation; D006801:Humans; D008958:Models, Molecular; D011110:Polymorphism, Genetic; D013379:Substrate Specificity; D015262:Xenobiotics / Q000378:metabolism
chemical_list: D015262:Xenobiotics; D001191:Arylamine N-Acetyltransferase