4rv7
From Proteopedia
Characterization of an essential diadenylate cyclase
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 PubMedThe 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. Structural and Biochemical Analysis of the Essential Diadenylate Cyclase CdaA from Listeria monocytogenes.,Rosenberg J, Dickmanns A, Neumann P, Gunka K, Arens J, Kaever V, Stulke J, Ficner R, Commichau FM J Biol Chem. 2015 Mar 6;290(10):6596-606. doi: 10.1074/jbc.M114.630418. Epub 2015, Jan 20. PMID:25605729[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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