A small step towards an important goal: fragment screen of the c-di-AMP-synthesizing enzyme CdaA


Neumann P, Heidemann JL, Wollenhaupt J, Dickmanns A, Agthe M, Weiss MS, Ficner R


Acta Crystallographica.Section D, Structural Biology


Acta Crystallogr D Struct Biol. 2024 May 1.


CdaA is the most widespread diadenylate cyclase in many bacterial species, including several multidrug-resistant human pathogens. The enzymatic product of CdaA, cyclic di-AMP, is a secondary messenger that is essential for the viability of many bacteria. Its absence in humans makes CdaA a very promising and attractive target for the development of new antibiotics. Here, the structural results are presented of a crystallographic fragment screen against CdaA from Listeria monocytogenes, a saprophytic Gram-positive bacterium and an opportunistic food-borne pathogen that can cause listeriosis in humans and animals. Two of the eight fragment molecules reported here were localized in the highly conserved ATP-binding site. These fragments could serve as potential starting points for the development of antibiotics against several CdaA-dependent bacterial species.


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