title: Structural and biochemical analysis of the essential diadenylate cyclase CdaA from Listeria monocytogenes.
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.
authors.affiliation: From the Departments of General Microbiology and.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Rosenberg
authors.affiliation: Molecular Structural Biology, Institute for Microbiology and Genetics, Georg-August University Göttingen, D-37077 Göttingen, Germany and.
authors.forename: Achim
authors.initials: A
authors.lastname: Dickmanns
authors.affiliation: Molecular Structural Biology, Institute for Microbiology and Genetics, Georg-August University Göttingen, D-37077 Göttingen, Germany and.
authors.forename: Piotr
authors.initials: P
authors.lastname: Neumann
authors.affiliation: From the Departments of General Microbiology and.
authors.forename: Katrin
authors.initials: K
authors.lastname: Gunka
authors.affiliation: Molecular Structural Biology, Institute for Microbiology and Genetics, Georg-August University Göttingen, D-37077 Göttingen, Germany and.
authors.forename: Johannes
authors.initials: J
authors.lastname: Arens
authors.affiliation: the Research Core Unit Metabolomics, Hannover Medical School, D-30625 Hannover, Germany.
authors.forename: Volkhard
authors.initials: V
authors.lastname: Kaever
authors.affiliation: From the Departments of General Microbiology and.
authors.forename: Jörg
authors.initials: J
authors.lastname: Stülke
authors.affiliation: Molecular Structural Biology, Institute for Microbiology and Genetics, Georg-August University Göttingen, D-37077 Göttingen, Germany and.
authors.forename: Ralf
authors.initials: R
authors.lastname: Ficner
authors.affiliation: From the Departments of General Microbiology and fcommic1@gwdg.de.
authors.forename: Fabian M
authors.initials: FM
authors.lastname: Commichau
mesh_terms: D000595:Amino Acid Sequence; D001412:Bacillus subtilis / Q000737:chemistry; D001426:Bacterial Proteins / Q000737:chemistry*; D002384:Catalysis; D002473:Cell Wall / Q000737:chemistry; D003035:Cobalt / Q000737:chemistry; D018360:Crystallography, X-Ray; D015226:Dinucleoside Phosphates / Q000378:metabolism; D006801:Humans; D008089:Listeria monocytogenes / Q000201:enzymology*; D019761:Phosphorus-Oxygen Lyases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation
chemical_list: D001426:Bacterial Proteins; D015226:Dinucleoside Phosphates; C528998:cyclic diadenosine phosphate; D003035:Cobalt; D019761:Phosphorus-Oxygen Lyases; C528997:diadenylate cyclase, Bacillus subtilis
keywords: Bacterial Signal Transduction; Crystal Structure; Cyclic Diadenosine Monophosphate (c-di-AMP); Enzyme Catalysis; Second Messenger