3E27

Nicotinic acid mononucleotide (NaMN) adenylyltransferase from Bacillus anthracis: product complex

3E27 の概要

• エントリーDOI: 10.2210/pdb3e27/pdb
• 分子名称: Nicotinate (Nicotinamide) nucleotide adenylyltransferase, NICOTINIC ACID ADENINE DINUCLEOTIDE, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: rossman-like fold, nucleotide-binding motif, nucleotidyltransferase, transferase
• 由来する生物種: Bacillus anthracis
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 90692.11

構造登録者

Martynowski, D.,Eyobo, Y.,Zhang, H. (登録日: 2008-08-05, 公開日: 2008-09-09, 最終更新日: 2023-08-30)

主引用文献

Sorci, L.,Pan, Y.,Eyobo, Y.,Rodionova, I.,Huang, N.,Kurnasov, O.,Zhong, S.,MacKerell, A.D.,Zhang, H.,Osterman, A.L.
Targeting NAD biosynthesis in bacterial pathogens: Structure-based development of inhibitors of nicotinate mononucleotide adenylyltransferase NadD.
Chem.Biol., 16:849-861, 2009

PubMed Abstract: The emergence of multidrug-resistant pathogens necessitates the search for new antibiotics acting on previously unexplored targets. Nicotinate mononucleotide adenylyltransferase of the NadD family, an essential enzyme of NAD biosynthesis in most bacteria, was selected as a target for structure-based inhibitor development. Using iterative in silico and in vitro screens, we identified small molecule compounds that efficiently inhibited target enzymes from Escherichia coli (ecNadD) and Bacillus anthracis (baNadD) but had no effect on functionally equivalent human enzymes. On-target antibacterial activity was demonstrated for some of the selected inhibitors. A 3D structure of baNadD was solved in complex with one of these inhibitors (3_02), providing mechanistic insights and guidelines for further improvement. Most importantly, the results of this study help validate NadD as a target for the development of antibacterial agents with potential broad-spectrum activity.

PubMed: 19716475
DOI: 10.1016/j.chembiol.2009.07.006

実験手法

X-RAY DIFFRACTION (2.2 Å)