6RBS

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

Summary for 6RBS

• Entry DOI: 10.2210/pdb6rbs/pdb
• Descriptor: NAD kinase 1, CITRIC ACID, 8-bromanyl-9-pent-4-ynyl-purin-6-amine, ... (4 entities in total)
• Functional Keywords: tetrameric nad kinase, transferase
• Biological source: Listeria monocytogenes serovar 1/2a (strain ATCC BAA-679 / EGD-e)
• Total number of polymer chains: 1
• Total formula weight: 31517.53

Authors

Gelin, M.,Labesse, G. (deposition date: 2019-04-11, release date: 2020-02-19, Last modification date: 2024-05-15)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.324 Å)