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J Biol Chem. 2019 Jul 5;294(27):10463-10470. doi: 10.1074/jbc.RA119.009246. Epub 2019 May 22.

Crystal structures of the c-di-AMP-synthesizing enzyme CdaA.

Author information

1
From the Department of Molecular Structural Biology, Institute for Microbiology and Genetics, Göttingen Center for Molecular Biosciences, Georg-August-University Göttingen, 37077 Göttingen, Germany.
2
From the Department of Molecular Structural Biology, Institute for Microbiology and Genetics, Göttingen Center for Molecular Biosciences, Georg-August-University Göttingen, 37077 Göttingen, Germany rficner@uni-goettingen.de.

Abstract

Cyclic di-AMP (c-di-AMP) is the only second messenger known to be essential for bacterial growth. It has been found mainly in Gram-positive bacteria, including pathogenic bacteria like Listeria monocytogenes CdaA is the sole diadenylate cyclase in L. monocytogenes, making this enzyme an attractive target for the development of novel antibiotic compounds. Here we report crystal structures of CdaA from L. monocytogenes in the apo state, in the post-catalytic state with bound c-di-AMP and catalytic Co2+ ions, as well as in a complex with AMP. These structures reveal the flexibility of a tyrosine side chain involved in locking the adenine ring after ATP binding. The essential role of this tyrosine was confirmed by mutation to Ala, leading to drastic loss of enzymatic activity.

KEYWORDS:

X-ray crystallography; cyclic di-AMP (c-di-AMP); metal ion–protein interaction; prokaryotic signal transduction; second messenger

PMID:
31118276
PMCID:
PMC6615682
[Available on 2020-07-05]
DOI:
10.1074/jbc.RA119.009246

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