8C4O

CdaA-ATP complex

Summary for 8C4O

• Entry DOI: 10.2210/pdb8c4o/pdb
• Descriptor: Diadenylate cyclase, MANGANESE (II) ION, ADENOSINE-5'-TRIPHOSPHATE, ... (6 entities in total)
• Functional Keywords: complex, protein binding
• Biological source: Listeria monocytogenes
• Total number of polymer chains: 2
• Total formula weight: 39977.14

Authors

Neumann, P.,Ficner, R. (deposition date: 2023-01-04, release date: 2023-06-07, Last modification date: 2024-06-19)

Primary citation

Neumann, P.,Kloskowski, P.,Ficner, R.
Computer-aided design of a cyclic di-AMP synthesizing enzyme CdaA inhibitor.
Microlife, 4:uqad021-uqad021, 2023

PubMed Abstract: Cyclic di-AMP (c-di-AMP) is an essential secondary messenger regulating cell wall homeostasis and myriads of physiological processes in several Gram-positive and mycobacteria, including human pathogens. Hence, c-di-AMP synthesizing enzymes (DACs) have become a promising antibacterial drug target. To overcome a scarcity of small molecule inhibitors of c-di-AMP synthesizing enzyme CdaA, a computer-aided design of a new compound that should block the enzyme has been performed. This has led to the identification of a molecule comprising two thiazole rings and showing inhibitory potential based on ITC measurements. Thiazole scaffold is a good pharmacophore nucleus known due to its various pharmaceutical applications. It is contained in more than 18 FDA-approved drugs as well as in dozens of experimental drugs. Hence, the designed inhibitor can serve as a potent lead compound for further development of inhibitor against CdaA.

PubMed: 37223749
DOI: 10.1093/femsml/uqad021

Experimental method

X-RAY DIFFRACTION (1.97 Å)