8c4p | pdb_00008c4p
CdaA-compound 7 complex
Structural highlights
FunctionDACA_LISMO Catalyzes the condensation of 2 ATP molecules into cyclic di-AMP (c-di-AMP), a signaling compound secreted into the host's cytosol where it triggers the cytosolic surveillance pathway (CSP), a host pathway of innate immunity characterized by expression of beta interferon (IFN-beta) and coregulated genes.[1] Publication Abstract from PubMedCyclic 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. Computer-aided design of a cyclic di-AMP synthesizing enzyme CdaA inhibitor.,Neumann P, Kloskowski P, Ficner R Microlife. 2023 Apr 14;4:uqad021. doi: 10.1093/femsml/uqad021. eCollection 2023. PMID:37223749[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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