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Publication Abstract from PubMed

The identification of the essential bacterial second messenger cyclic-di-AMP synthesized by the DNA-integrity scanning protein DisA opened up a new and emerging field in bacterial signaling. To further analyze the di-adenylate cyclase reaction catalyzed by the DAC domains of DisA, we crystallized Thermotoga maritima DisA in presence of different ATP analogs and metal ions to identify the metal binding site and trap the enzyme in pre- and post-reaction states. Through structural and biochemical assays we identified important residues essential for the reaction in the active site of the DAC domains. Our structures resolve the metal binding site and thus explain the activation of ATP for the DAC reaction. Moreover, we were able to identify a potent inhibitor of the DAC domain. Based on the available structures and homology to annotated DAC domains we propose a common mechanism for c-di-AMP synthesis by DAC domains in c-di-AMP producing species and a possible approach for its effective inhibition.

Structural analysis of the di-adenylate cyclase reaction of DNA-integrity scanning protein A (DisA) and its inhibition by 3'-dATP.,Muller M, Deimling T, Hopfner KP, Witte G Biochem J. 2015 May 27. PMID:26014055^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.