4RV7

Characterization of an essential diadenylate cyclase

Summary for 4RV7

• Entry DOI: 10.2210/pdb4rv7/pdb
• Descriptor: Diadenylate cyclase, ADENOSINE-5'-TRIPHOSPHATE, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: dac-fold, atp binding, c-di-amp binding, transferase
• Biological source: Listeria monocytogenes EGD-e
• Total number of polymer chains: 4
• Total formula weight: 86247.35

Authors

Dickmanns, A.,Neumann, P.,Ficner, R. (deposition date: 2014-11-25, release date: 2015-01-28, Last modification date: 2023-09-20)

Primary citation

Rosenberg, J.,Dickmanns, A.,Neumann, P.,Gunka, K.,Arens, J.,Kaever, V.,Stulke, J.,Ficner, R.,Commichau, F.M.
Structural and Biochemical Analysis of the Essential Diadenylate Cyclase CdaA from Listeria monocytogenes.
J.Biol.Chem., 290:6596-6606, 2015

PubMed Abstract: The recently identified second messenger cyclic di-AMP (c-di-AMP) is involved in several important cellular processes, such as cell wall metabolism, maintenance of DNA integrity, ion transport, transcription regulation, and allosteric regulation of enzyme function. Interestingly, c-di-AMP is essential for growth of the Gram-positive model bacterium Bacillus subtilis. Although the genome of B. subtilis encodes three c-di-AMP-producing diadenlyate cyclases that can functionally replace each other, the phylogenetically related human pathogens like Listeria monocytogenes and Staphylococcus aureus possess only one enzyme, the diadenlyate cyclase CdaA. Because CdaA is also essential for growth of these bacteria, the enzyme is a promising target for the development of novel antibiotics. Here we present the first crystal structure of the L. monocytogenes CdaA diadenylate cyclase domain that is conserved in many human pathogens. Moreover, biochemical characterization of the cyclase revealed an unusual metal cofactor requirement.

PubMed: 25605729
DOI: 10.1074/jbc.M114.630418

Experimental method

X-RAY DIFFRACTION (2.8 Å)