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The analysis of the optimized structures of the MichaelisMenten complex indicate that the polar residues at position 13 (Cys or Ser) stabilize the deprotonated GS , which in turn acts as the catalytic Brnsted base and abstracts the proton at position C2 of substrate 7 (Extended Data Fig

The 1-methylnicotinamide product of NNMT may itself have biological activities (including potential insulin resistance-promoting effects), and reducing its production through NNMT inhibition may contribute to metabolic improvements

But the current regulatory framework disagrees

Wang Y, Hou Y, Qiu J, Wang H, Wang S, Tang L, Tong X, Zhang J

Through non-metabolic regulatory pathways, it directly participates in inflammatory activation and fibrosis progression, playing a pivotal role in the pathogenesis of DKD [34]

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