NMR-based model reveals the structural determinants of mammalian arylamine N-acetyltransferase substrate specificity.

NMR-based model reveals the structural determinants of mammalian arylamine N-acetyltransferase substrate specificity. Research Abstract Details 

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NMR-based model reveals the structural determinants of mammalian arylamine N-acetyltransferase substrate specificity. Abstract Text:

Naixia Zhang,Li Liu,Fen Liu,Carston R Wagner,Patrick E Hanna,Kylie J Walters,

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. Publishing Authors By Initials

N Zhang,L Liu,F Liu,CR Wagner,PE Hanna,KJ Walters,

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NMR-based model reveals the structural determinants of mammalian arylamine N-acetyltransferase substrate specificity. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Journal of molecular biology

VOLUME: 363

Page Numbers: 188-200

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ISSN: 0022-2836

DAY: 15

MONTH: 08

YEAR: 2006

NMR-based model reveals the structural determinants of mammalian arylamine N-acetyltransferase substrate specificity. Information

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LANGUAGE: eng

NlmUniqueID: 2985088

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Grant and Affiliation Information for NMR-based model reveals the structural determinants of mammalian arylamine N-acetyltransferase substrate specificity.

AFFILIATION: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.

Country: England

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MEDLINETA: J Mol Biol

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