Gene/Protein Disease Symptom Drug Enzyme Compound
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Carbon black nanoparticles (CB NPs) and their respirable aggregates/agglomerates are classified as possibly carcinogenic to humans. In certain industrial work settings, CB NPs coexist with aromatic amines (AA), which comprise a major class of human carcinogens. It is therefore crucial to characterize the interactions of CB NPs with AA-metabolizing enzymes. Here, we report molecular and cellular evidence that CB NPs interfere with the enzymatic acetylation of carcinogenic AA by rapidly binding to arylamine N-acetyltransferase (NAT), the major AA-metabolizing enzyme. Kinetic and biophysical analyses showed that this interaction leads to protein conformational changes and an irreversible loss of enzyme activity. In addition, our data showed that exposure to CB NPs altered the acetylation of 2-aminofluorene in intact lung Clara cells by impairing the endogenous NAT-dependent pathway. This process may represent an additional mechanism that contributes to the carcinogenicity of inhaled CB NPs. Our results add to recent data suggesting that major xenobiotic detoxification pathways may be altered by certain NPs and that this can result in potentially harmful pharmacological and toxicological effects.
ACS Nano 2011 Jun 28
PMID:Carbon black nanoparticles impair acetylation of aromatic amine carcinogens through inactivation of arylamine N-acetyltransferase enzymes. 2152 48

Mapping proteins at a specific subcellular location is essential to gaining detailed insight on local protein dynamics. We have developed an enzymatic strategy to label proteins on a subcellular level using arylamine N-acetyltransferase (NAT). The NAT enzyme activates an arylhydroxamic acid functionality into a nitrenium ion that reacts fast, covalently, and under neutral conditions with nucleophilic residues of neighboring proteins. The electron density on the aromatic ring proved important for probe activation as strong labeling was only observed with an arylhydroxamic acid bearing an electron donating substituent. We further demonstrate that, using this electron rich arylhydroxamic acid, clear labeling was achieved on a subcellular level in living cells that were transfected with a genetically targeted NAT to the nucleus or the cytosol.
ACS Chem Biol 2018 08 17
PMID:Subcellular Protein Labeling by a Spatially Restricted Arylamine N-Acetyltransferase. 3065 55