6Z61

Crystal structure of NAD kinase 1 from Listeria monocytogenes in complex with a di-adenosine derivative

6Z61 の概要

• エントリーDOI: 10.2210/pdb6z61/pdb
• 分子名称: NAD kinase 1, CITRIC ACID, (2~{R},3~{R},4~{S},5~{R})-2-[6-azanyl-8-[3-[[(2~{R},3~{S},4~{R},5~{R})-5-[6-(2-azanylethylamino)purin-9-yl]-3,4-bis(oxidanyl)oxolan-2-yl]methoxy]prop-1-ynyl]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol, ... (4 entities in total)
• 機能のキーワード: tetrameric nad-kinase, transferase
• 由来する生物種: Listeria monocytogenes EGD-e
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 31850.99

構造登録者

Gelin, M.,Labesse, G. (登録日: 2020-05-27, 公開日: 2021-05-26, 最終更新日: 2024-01-24)

主引用文献

Clement, D.A.,Leseigneur, C.,Gelin, M.,Coelho, D.,Huteau, V.,Lionne, C.,Labesse, G.,Dussurget, O.,Pochet, S.
New Chemical Probe Targeting Bacterial NAD Kinase.
Molecules, 25:-, 2020

PubMed Abstract: Nicotinamide adenine dinucleotide (NAD) kinases are essential and ubiquitous enzymes involved in the tight regulation of NAD/nicotinamide adenine dinucleotide phosphate (NADP) levels in many metabolic pathways. Consequently, they represent promising therapeutic targets in cancer and antibacterial treatments. We previously reported diadenosine derivatives as NAD kinase inhibitors with bactericidal activities on . Among them, one compound (namely ) was found effective in vivo in a mouse infection model. With the aim to gain detailed knowledge about the selectivity and mechanism of action of this lead compound, we planned to develop a chemical probe that could be used in affinity-based chemoproteomic approaches. Here, we describe the first functionalized chemical probe targeting a bacterial NAD kinase. Aminoalkyl functional groups were introduced on for further covalent coupling to an activated Sepharose matrix. Inhibitory properties of functionalized derivatives together with X-ray characterization of their complexes with the NAD kinase led to identify candidate compounds that are amenable to covalent coupling to a matrix.

PubMed: 33105870
DOI: 10.3390/molecules25214893

実験手法

X-RAY DIFFRACTION (2.47 Å)