Arylamine N-acetyltransferases: a structural perspective

Br J Pharmacol. 2013 Jun;169(4):748-60. doi: 10.1111/bph.12182.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acetylation / drug effects
  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology
  • Arylamine N-Acetyltransferase / antagonists & inhibitors
  • Arylamine N-Acetyltransferase / chemistry*
  • Arylamine N-Acetyltransferase / genetics
  • Arylamine N-Acetyltransferase / metabolism
  • Bacterial Proteins / antagonists & inhibitors
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Biocatalysis / drug effects
  • Biotransformation / drug effects
  • Catalytic Domain / drug effects
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacology
  • Heterocyclic Compounds / chemistry
  • Heterocyclic Compounds / metabolism
  • Heterocyclic Compounds / pharmacokinetics
  • Humans
  • Hydrocarbons, Aromatic / chemistry
  • Hydrocarbons, Aromatic / metabolism
  • Hydrocarbons, Aromatic / pharmacokinetics
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / chemistry*
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Models, Molecular*
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Polymorphism, Genetic
  • Protein Conformation
  • Substrate Specificity

Substances

  • Antineoplastic Agents
  • Bacterial Proteins
  • Enzyme Inhibitors
  • Heterocyclic Compounds
  • Hydrocarbons, Aromatic
  • Isoenzymes
  • Neoplasm Proteins
  • Arylamine N-Acetyltransferase
  • N-acetyltransferase 1
  • NAT2 protein, human