6RC2

Crystal structure of NAD kinase 1 from Listeria monocytogenes in complexe with an adenine derivative

6RC2 の概要

• エントリーDOI: 10.2210/pdb6rc2/pdb
• 分子名称: NAD kinase 1, CITRIC ACID, 8-methyl-9-pent-4-ynyl-purin-6-amine, ... (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: 31452.66

構造登録者

Gelin, M.,Labesse, G. (登録日: 2019-04-11, 公開日: 2020-02-19, 最終更新日: 2024-05-15)

主引用文献

Gelin, M.,Paoletti, J.,Nahori, M.A.,Huteau, V.,Leseigneur, C.,Jouvion, G.,Dugue, L.,Clement, D.,Pons, J.L.,Assairi, L.,Pochet, S.,Labesse, G.,Dussurget, O.
From Substrate to Fragments to Inhibitor ActiveIn VivoagainstStaphylococcus aureus.
Acs Infect Dis., 6:422-435, 2020

PubMed Abstract: Antibiotic resistance is a worldwide threat due to the decreasing supply of new antimicrobials. Novel targets and innovative strategies are urgently needed to generate pathbreaking drug compounds. NAD kinase (NADK) is essential for growth in most bacteria, as it supports critical metabolic pathways. Here, we report the discovery of a new class of antibacterials that targets bacterial NADK. We generated a series of small synthetic adenine derivatives to screen those harboring promising substituents in order to guide efficient fragment linking. This led to NKI1, a new lead compound inhibiting NADK that showed bactericidal activity against . In a murine model of infection, NKI1 restricted survival of the bacteria, including methicillin-resistant . Collectively, these findings identify bacterial NADK as a potential drug target and NKI1 as a lead compound in the treatment of staphylococcal infections.

PubMed: 32017533
DOI: 10.1021/acsinfecdis.9b00368

実験手法

X-RAY DIFFRACTION (2.048 Å)