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J Biol Chem. 2015 Mar 6;290(10):6596-606. doi: 10.1074/jbc.M114.630418. Epub 2015 Jan 20.

Structural and biochemical analysis of the essential diadenylate cyclase CdaA from Listeria monocytogenes.

Author information

1
From the Departments of General Microbiology and.
2
Molecular Structural Biology, Institute for Microbiology and Genetics, Georg-August University Göttingen, D-37077 Göttingen, Germany and.
3
the Research Core Unit Metabolomics, Hannover Medical School, D-30625 Hannover, Germany.
4
From the Departments of General Microbiology and fcommic1@gwdg.de.

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.

KEYWORDS:

Bacterial Signal Transduction; Crystal Structure; Cyclic Diadenosine Monophosphate (c-di-AMP); Enzyme Catalysis; Second Messenger

PMID:
25605729
PMCID:
PMC4358292
DOI:
10.1074/jbc.M114.630418
[Indexed for MEDLINE]
Free PMC Article

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