4YXM: Structure Of Thermotoga Maritima Disa D75n Mutant With Reaction Product C-di-amp

Citation:
Abstract
The identification of the essential bacterial second messenger cyclic-di-AMP (c-di-AMP) synthesized by the DNA-integrity scanning protein A (DisA) has opened up a new and emerging field in bacterial signalling. To further analyse the diadenylate cyclase (DAC) reaction catalysed by the DAC domains of DisA, we crystallized Thermotoga maritima DisA in the presence of different ATP analogues 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.
PDB ID: 4YXMDownload
MMDB ID: 129794
PDB Deposition Date: 2015/3/23
Updated in MMDB: 2017/09
Experimental Method:
x-ray diffraction
Resolution: 2.25  Å
Source Organism:
Similar Structures:
Biological Unit for 4YXM: octameric; determined by author and by software (PISA)
Molecular Components in 4YXM
Label Count Molecule
Proteins (8 molecules)
8
DNA Integrity Scanning Protein Disa(Gene symbol: TM0200)
Molecule annotation
Chemicals (8 molecules)
1
4
2
4
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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