4YXJ

Structure of Thermotoga maritima DisA in complex with ApCpp

Summary for 4YXJ

• Entry DOI: 10.2210/pdb4yxj/pdb
• Related: 3c1y 3c1z 3c21 3c23 4YVZ
• Descriptor: DNA integrity scanning protein DisA, DIPHOSPHOMETHYLPHOSPHONIC ACID ADENOSYL ESTER (3 entities in total)
• Functional Keywords: dna binding protein, c-di-amp synthesis, dac domain, inhibitor, pre-reaction state, transferase
• Biological source: Thermotoga maritima
• Total number of polymer chains: 2
• Total formula weight: 86538.38

Authors

Mueller, M.,Deimling, T.,Hopfner, K.-P.,Witte, G. (deposition date: 2015-03-23, release date: 2015-06-03, Last modification date: 2024-01-10)

Primary citation

Muller, M.,Deimling, T.,Hopfner, K.P.,Witte, G.
Structural analysis of the diadenylate cyclase reaction of DNA-integrity scanning protein A (DisA) and its inhibition by 3'-dATP.
Biochem.J., 469:367-374, 2015

PubMed 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.

PubMed: 26014055
DOI: 10.1042/BJ20150373

Experimental method

X-RAY DIFFRACTION (2.55 Å)