5XVK
Crystal structure of mouse Nicotinamide N-methyltransferase (NNMT) bound with end product, 1-methyl Nicotinamide (MNA)
Summary for 5XVK
Entry DOI | 10.2210/pdb5xvk/pdb |
Descriptor | Nicotinamide N-methyltransferase, S-ADENOSYL-L-HOMOCYSTEINE, 3-carbamoyl-1-methylpyridin-1-ium, ... (5 entities in total) |
Functional Keywords | nnmt, mna, ternary complex, feedback inhibition, t2d, transferase |
Biological source | Mus musculus (Mouse) |
Total number of polymer chains | 2 |
Total formula weight | 64735.46 |
Authors | Swaminathan, S.,Birudukota, S.,Thakur, M.K.,Parveen, R.,Kandan, S.,Kannt, A.,Gosu, R. (deposition date: 2017-06-28, release date: 2017-08-02, Last modification date: 2023-11-22) |
Primary citation | Swaminathan, S.,Birudukota, S.,Thakur, M.K.,Parveen, R.,Kandan, S.,Juluri, S.,Shaik, S.,Anand, N.N.,Burri, R.R.,Kristam, R.,Hallur, M.S.,Rajagopal, S.,Schreuder, H.,Langer, T.,Rudolph, C.,Ruf, S.,Dhakshinamoorthy, S.,Gosu, R.,Kannt, A. Crystal structures of monkey and mouse nicotinamide N-methyltransferase (NNMT) bound with end product, 1-methyl nicotinamide Biochem. Biophys. Res. Commun., 491:416-422, 2017 Cited by PubMed Abstract: Nicotinamide N-methyltransferase (NNMT) is a S-adenosyl-l-methionine (SAM)-dependent enzyme that catalyzes N-methylation of nicotinamide (NA) and other pyridines to form N-methyl pyridinium ions. Here we report the first ternary complex X-ray crystal structures of monkey NNMT and mouse NNMT in bound form with the primary endogenous product, 1-methyl nicotinamide (MNA) and demethylated cofactor, S-adenosyl-homocysteine (SAH) determined at 2.30 Å and 1.88 Å respectively. The structural fold of these enzymes is identical to human NNMT. It is known that the primary endogenous product catalyzed by NNMT, MNA is a specific inhibitor of NNMT. Our data clearly indicates that the MNA binds to the active site and it would be trapped in the active site due to the formation of the bridge between the pole (long helix, α3) and long C-terminal loop. This might explain the mechanism of MNA acting as a feedback inhibitor of NNMT. PubMed: 28720493DOI: 10.1016/j.bbrc.2017.07.087 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (1.88 Å) |
Structure validation
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