5XVK

Crystal structure of mouse Nicotinamide N-methyltransferase (NNMT) bound with end product, 1-methyl Nicotinamide (MNA)

5XVK の概要

• エントリーDOI: 10.2210/pdb5xvk/pdb
• 分子名称: Nicotinamide N-methyltransferase, S-ADENOSYL-L-HOMOCYSTEINE, 3-carbamoyl-1-methylpyridin-1-ium, ... (5 entities in total)
• 機能のキーワード: nnmt, mna, ternary complex, feedback inhibition, t2d, transferase
• 由来する生物種: Mus musculus (Mouse)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 64735.46

構造登録者

Swaminathan, S.,Birudukota, S.,Thakur, M.K.,Parveen, R.,Kandan, S.,Kannt, A.,Gosu, R. (登録日: 2017-06-28, 公開日: 2017-08-02, 最終更新日: 2023-11-22)

主引用文献

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

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: 28720493
DOI: 10.1016/j.bbrc.2017.07.087

実験手法

X-RAY DIFFRACTION (1.88 Å)