Structural highlights
Publication Abstract from PubMed
Arylamine N-acetyltransferases (NATs) catalyze the acetylation of arylamines, a key step in the detoxification of many carcinogens. The determinants of NAT substrate specificity are not known, yet this knowledge is required to understand why NAT enzymes acetylate some arylamines, but not others. Here, we use NMR spectroscopy and homology modeling to reveal the structural determinants of arylamine acetylation by NATs. In particular, by using chemical shift perturbation analysis, we have identified residues that play a critical role in substrate binding and catalysis. This study reveals why human NAT1 acetylates the sunscreen additive p-aminobenzoic acid and tobacco smoke carcinogen 4-aminobiphenyl, but not o-toluidine and other arylamines linked to bladder cancer. Our results represent an important step toward predicting whether arylamines present in new products can be detoxified by mammalian NATs.
NMR-based model reveals the structural determinants of mammalian arylamine N-acetyltransferase substrate specificity.,Zhang N, Liu L, Liu F, Wagner CR, Hanna PE, Walters KJ J Mol Biol. 2006 Oct 13;363(1):188-200. Epub 2006 Aug 15. PMID:16959263[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Zhang N, Liu L, Liu F, Wagner CR, Hanna PE, Walters KJ. NMR-based model reveals the structural determinants of mammalian arylamine N-acetyltransferase substrate specificity. J Mol Biol. 2006 Oct 13;363(1):188-200. Epub 2006 Aug 15. PMID:16959263 doi:10.1016/j.jmb.2006.08.026
