A Rapid and Efficient Assay for the Characterization of Substrates and Inhibitors of Nicotinamide N-Methyltransferase

Biochemistry
Matthijs J van HarenNathaniel I Martin

Abstract

Nicotinamide N-methyltransferase (NNMT) is one of the most abundant small molecule methyltransferases in the human body and is primarily responsible for the N-methylation of the nicotinamide (vitamin B3). Employing the cofactor S-adenosyl-l-methionine, NNMT transfers a methyl group to the pyridine nitrogen of nicotinamide to generate N-methylnicotinamide. Interestingly, NNMT is also able to N-methylate a variety of other pyridine-containing small molecules, suggesting a secondary role for the enzyme in the detoxification of xenobiotics. A number of recent studies have also revealed links between NNMT overexpression and a variety of diseases, including multiple cancers, Parkinson's disease, diabetes, and obesity. To facilitate further study of both the substrate scope and potential for inhibitor development, we here describe the development of a new NNMT activity assay. The assay makes use of ultra-high-performance hydrophilic interaction chromatography, allowing for rapid separation of the reaction products, coupled with quadrupole time-of-flight mass spectrometric detection, providing for enhanced sensitivity and enabling high-throughput sample analysis. We successfully demonstrated the general applicability of the method by p...Continue Reading

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Citations

May 27, 2017·Journal of Medicinal Chemistry·Harshini NeelakantanStanley J Watowich
Aug 1, 2017·Organic & Biomolecular Chemistry·Matthijs J van HarenNathaniel I Martin
Feb 9, 2018·Melanoma Research·Giulia GanzettiMonica Emanuelli
Feb 28, 2018·Scientific Reports·Aimo KanntSaravanakumar Dhakshinamoorthy
Mar 1, 2018·Pharmacological Reviews·Fabian MüllerMartin F Fromm
Oct 17, 2017·Endocrine Research·Bianca RudolphiDaniel Kraus

Related Concepts

Proteins, Recombinant DNA
Substrate Specificity
Nicotinamide N-Methyltransferase
Diabetes
Methylation
Niacin
Nitrogen
Obesity
Parkinson Disease
Pyridine

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