Thompson Lab's Heather Loring Publishes Paper in ACS Biochemistry

Date Posted: Wednesday, September 05, 2018

Nicotinamide N-MethyltransferaseNicotinamide N-methyltransferase (NNMT) catalyzes the irreversible methylation of nicotinamide (NAM), pyridine and other structural analogs by utilizing S-adenosyl methionine (SAM) as a methyl donor. Aberrantly increased NNMT activity alters the epigenetic profile and disrupts energy metabolism. As a result, NNMT is implicated in cancer, neurodegenerative diseases and metabolic diseases, making it an appealing target for therapeutic intervention. To gain insights that would guide the design therapeutics targeting this enzyme, we performed detailed kinetic studies on human NNMT.  For the first time, we report the kinetic mechanism of NNMT. Our studies collectively indicate that NNMT uses a rapid equilibrium ordered mechanism, where NNMT first binds SAM, which is followed by NAM. Methyltransfer subsequently occurs and methylated NAM (MeNAM) and S-adenosyl homocysteine (SAH) are released consecutively. 

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