Journal
JOURNAL OF MOLECULAR BIOLOGY
Volume 363, Issue 1, Pages 188-200Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2006.08.026
Keywords
arylamine N-acetyltransferase; substrate specificity; arylamine carcinogens; structural determinants; NMR
Categories
Funding
- NCI NIH HHS [CA097004-01A1] Funding Source: Medline
Ask authors/readers for more resources
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 paminobenzoic 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. (c) 2006 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available