Co-crystal structure of Human Nicotinamide N-methyltransferase (NNMT) with the bisubstrate-like inhibitor (33)

Novel Inhibitors of Nicotinamide- N -Methyltransferase for the Treatment of Metabolic Disorders.

MGSSHHHHHHSSGLVPRGSMESGFTSKDTYLSHFNPRDYLEKYYKFGSRHSAESQILKHLLKNLFKIFCLDGVKGDLLID
IGSGPTIYQLLSACESFKEIVVTDYSDQNLQELEKWLKAAPAAFDWSPVVTYVCDLEGNRVKGPEKEEKLRQAVKQVLKC
DVTQSQPLGAVPLPPADCVLSTLCLDAACPDLPTYCRALRNLGSLLKPGGFLVIMDALKSSYYMIGEQKFSSLPLGREAV
EAAVKEAGYTIEWFEVISQSYSSTMANNEGLFSLVARKLSRPL

Human NNMT was crystallized using the following conditions: A protein solution with 6 mg/ml NNMT, 50 mM Tris/HCL, pH 8.0, 1 mM DTT, 0.95mM inhibitor and 5% v/v glycerol was equilibrated at room temperature in a hanging drop setup against 2.2 M ammonium sulfate with 0.1 M HEPES/Na, pH 7.6. Small crystal appeared after 1-2 weeks.

Methyl Transferase, drug discovery, Inhibitor complex, Nicotinamide, metabolic disorders, TRANSFERASE

MESGFTSKDTYLSHFNPRDYLEKYYKFGSRHSAESQILKHLLKNLFKIFCLDGVKGDLLIDIGSGPTIYQLLSACESFKE
IVVTDYSDQNLQELEKWLKKEPEAFDWSPVVTYVCDLEGNRVKGPEKEEKLRQAVKQVLKCDVTQSQPLGAVPLPPADCV
LSTLCLDAACPDLPTYCRALRNLGSLLKPGGFLVIMDALKSSYYMIGEQKFSSLPLGREAVEAAVKEAGYTIEWFEVISQ
SYSSTMANNEGLFSLVARKLSRPL