title: Eubacterial arylamine N-acetyltransferases - identification and comparison of 18 members of the protein family with conserved active site cysteine, histidine and aspartate residues.
abstract: Arylamine N-acetyltransferases (NATs) are enzymes involved in the detoxification of a range of arylamine and hydrazine-based xenobiotics. NATs have been implicated in the endogenous metabolism of p-aminobenzoyl glutamate in eukaryotes, although very little is known about the distribution and function of NAT in the prokaryotic kingdom. Using DNA library screening techniques and the analysis of data from whole-genome sequencing projects, we have identified 18 nat-like sequences from the Proteobacteria and Firmicutes. Recently, the three-dimensional structure of NAT derived from the bacterium Salmonella typhimurium (PDB accession code 1E2T) was resolved and revealed an active site catalytic triad composed of Cys(69)-His(107)-Asp(122). These residues have been shown to be conserved in all prokaryotic and eukaryotic NAT homologues together with three highly conserved regions which are found proximal to the active site triad. The characterization of prokaryotic NATs and NAT-like enzymes is reported. It is also predicted that prokaryotic NATs, based on gene cluster composition and distribution amongst genomes, participate in the metabolism of xenobiotics derived from decomposition of organic materials.
authors.affiliation: Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK1.
authors.forename: Mark
authors.initials: M
authors.lastname: Payton
authors.affiliation: Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK1.
authors.forename: Adeel
authors.initials: A
authors.lastname: Mushtaq
authors.affiliation: Department of Chemistry, Box 351700, University of Washington, Seattle, WA 98195-1700, USA2.
authors.forename: Tin-Wein
authors.initials: TW
authors.lastname: Yu
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK3.
authors.forename: Ling-Juan
authors.initials: LJ
authors.lastname: Wu
authors.affiliation: The Laboratory of Molecular Biophysics, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK4.
authors.forename: John
authors.initials: J
authors.lastname: Sinclair
authors.affiliation: Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK1.
authors.forename: Edith
authors.initials: E
authors.lastname: Sim
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001191:Arylamine N-Acetyltransferase / Q000737:chemistry*; D001224:Aspartic Acid / Q000737:chemistry; D001426:Bacterial Proteins / Q000737:chemistry*; D015153:Blotting, Western; D020134:Catalytic Domain; D017124:Conserved Sequence; D003545:Cysteine / Q000737:chemistry; D004755:Enterobacteriaceae / Q000201:enzymology* / Q000235:genetics; D006094:Gram-Positive Bacteria / Q000201:enzymology* / Q000235:genetics; D006639:Histidine / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009876:Operon; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D020560:Proteobacteria / Q000201:enzymology* / Q000235:genetics; D016415:Sequence Alignment; D013379:Substrate Specificity
chemical_list: D001426:Bacterial Proteins; D001224:Aspartic Acid; D006639:Histidine; D001191:Arylamine N-Acetyltransferase; D003545:Cysteine