title: Arylamine N-acetyltransferases: a structural perspective.
abstract: Arylamine N-acetyltransferase (NAT) plays an important role in metabolism and detoxification of many compounds including drugs and environmental carcinogens through chemical modification of the amine group with an acetyl group. Recent studies have suggested that NATs are also involved in cancer cell growth and inhibition of the enzymes may be a potential target for cancer chemotherapy. Three-dimensional (3D) structures are available for NATs from both prokaryotes and eukaryotes. These structures provide valuable insights into the acetylation mechanism, features of the active site and the structural determinants that govern substrate/inhibitor-binding specificity. Such insights allow a more precise understanding of the structure-activity relationships for NAT substrates and inhibitors. Furthermore, the structural elucidation of NATs has generated powerful tools in the design of small molecule inhibitors that should alleviate cancer, based on the important role of the enzyme in cancer biology.
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, Jinan University, Guangzhou, Guangdong, China.
authors.forename: Xiaotong
authors.initials: X
authors.lastname: Zhou
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Ma
authors.forename: Dong
authors.initials: D
authors.lastname: Dong
authors.forename: Baojian
authors.initials: B
authors.lastname: Wu
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001191:Arylamine N-Acetyltransferase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D055162:Biocatalysis / Q000187:drug effects; D001711:Biotransformation / Q000187:drug effects; D020134:Catalytic Domain / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D006801:Humans; D006841:Hydrocarbons, Aromatic / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011110:Polymorphism, Genetic; D011487:Protein Conformation; D013379:Substrate Specificity
chemical_list: D000970:Antineoplastic Agents; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D006571:Heterocyclic Compounds; D006841:Hydrocarbons, Aromatic; D007527:Isoenzymes; D009363:Neoplasm Proteins; D001191:Arylamine N-Acetyltransferase; C089384:N-acetyltransferase 1; C478900:NAT2 protein, human