8IGZ

Xcc NAMPT Quadruple mutant

8IGZ の概要

• エントリーDOI: 10.2210/pdb8igz/pdb
• 分子名称: Pre-B cell enhancing factor related protein (1 entity in total)
• 機能のキーワード: xcc nampt mutant, transferase
• 由来する生物種: Xanthomonas campestris pv. campestris str. 8004
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 106677.70

構造登録者

Xu, G.L.,Ming, Z.H. (登録日: 2023-02-21, 公開日: 2024-02-28, 最終更新日: 2024-05-22)

主引用文献

Xu, G.,Ma, J.,Fang, Q.,Peng, Q.,Jiao, X.,Hu, W.,Zhao, Q.,Kong, Y.,Liu, F.,Shi, X.,Tang, D.J.,Tang, J.L.,Ming, Z.
Structural insights into Xanthomonas campestris pv. campestris NAD + biosynthesis via the NAM salvage pathway.
Commun Biol, 7:255-255, 2024

PubMed Abstract: Nicotinamide phosphoribosyltransferase (NAMPT) plays an important role in the biosynthesis of nicotinamide adenine dinucleotide (NAD) via the nicotinamide (NAM) salvage pathway. While the structural biochemistry of eukaryote NAMPT has been well studied, the catalysis mechanism of prokaryote NAMPT at the molecular level remains largely unclear. Here, we demonstrated the NAMPT-mediated salvage pathway is functional in the Gram-negative phytopathogenic bacterium Xanthomonas campestris pv. campestris (Xcc) for the synthesis of NAD, and the enzyme activity of NAMPT in this bacterium is significantly higher than that of human NAMPT in vitro. Our structural analyses of Xcc NAMPT, both in isolation and in complex with either the substrate NAM or the product nicotinamide mononucleotide (NMN), uncovered significant details of substrate recognition. Specifically, we revealed the presence of a NAM binding tunnel that connects the active site, and this tunnel is essential for both catalysis and inhibitor binding. We further demonstrated that NAM binding in the tunnel has a positive cooperative effect with NAM binding in the catalytic site. Additionally, we discovered that phosphorylation of the His residue at position 229 enhances the substrate binding affinity of Xcc NAMPT and is important for its catalytic activity. This work reveals the importance of NAMPT in bacterial NAD synthesis and provides insights into the substrate recognition and the catalytic mechanism of bacterial type II phosphoribosyltransferases.

PubMed: 38429435
DOI: 10.1038/s42003-024-05921-3

実験手法

X-RAY DIFFRACTION (3.11 Å)