Eubacterial arylamine N-acetyltransferases - identification and comparisonof 18 members of the protein family with conserved active site cysteine, histidine and aspartate residues

Arylamine N-acetyltransferases (NATs) are enzymes involved in the detoxific ation of a range of arylamine and hydrazine-based xenobiotics. NATs have be en implicated in the endogenous metabolism of p-aminobenzoyl glutamate in e ukaryotes, although very little is known about the distribution and functio n of NAT in the prokaryotic kingdom. Using DNA library screening techniques and the analysis of data from whole-genome sequencing projects, we have id entified 18 nat-like sequences from the Proteobacteria and Firmicutes. Rece ntly, the three-dimensional structure of NAT derived from the bacterium Sal monella typhimurium (PDB accession code 1E2T) was resolved and revealed an active site catalytic triad composed of Cys(69)-His(107)-Asp(122). These re sidues have been shown to be conserved in all prokaryotic and eukaryotic NA T homologues together with three highly conserved regions which are found p roximal to the active site triad, The characterization of prokaryotic NATs and NAT-like enzymes is reported. It is also predicted that prokaryotic NAT s, based on gene cluster composition and distribution amongst genomes, part icipate in the metabolism of xenobiotics derived from decomposition of orga nic materials.