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4yxm

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Structure of Thermotoga maritima DisA D75N mutant with reaction product c-di-AMP

Structural highlights

4yxm is a 2 chain structure with sequence from Thermotoga maritima. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.25Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DISA_THEMA Participates in a DNA-damage check-point. DisA forms globular foci that rapidly scan along the chromosomes searching for lesions (By similarity).^[1] Has also diadenylate cyclase activity, catalyzing the condensation of 2 ATP molecules into cyclic di-AMP (c-di-AMP). c-di-AMP likely acts as a signaling molecule that may couple DNA integrity with a cellular process. Does not convert GTP to c-di-GMP.^[2]

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.

References

↑ Witte G, Hartung S, Buttner K, Hopfner KP. Structural biochemistry of a bacterial checkpoint protein reveals diadenylate cyclase activity regulated by DNA recombination intermediates. Mol Cell. 2008 Apr 25;30(2):167-78. PMID:18439896 doi:10.1016/j.molcel.2008.02.020
↑ Witte G, Hartung S, Buttner K, Hopfner KP. Structural biochemistry of a bacterial checkpoint protein reveals diadenylate cyclase activity regulated by DNA recombination intermediates. Mol Cell. 2008 Apr 25;30(2):167-78. PMID:18439896 doi:10.1016/j.molcel.2008.02.020
↑ Muller M, Deimling T, Hopfner KP, Witte G. Structural analysis of the di-adenylate cyclase reaction of DNA-integrity scanning protein A (DisA) and its inhibition by 3'-dATP. Biochem J. 2015 May 27. PMID:26014055 doi:http://dx.doi.org/10.1042/BJ20150373

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4yxm"

@@ Line 1: / Line 1: @@
 ==Structure of Thermotoga maritima DisA D75N mutant with reaction product c-di-AMP==
-<StructureSection load='4yxm' size='340' side='right' caption='[[4yxm]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
+<StructureSection load='4yxm' size='340' side='right'caption='[[4yxm]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4yxm]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YXM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YXM FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4yxm]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Thermotoga_maritima Thermotoga maritima]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YXM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YXM FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2BA:(2R,3R,3AS,5R,7AR,9R,10R,10AS,12R,14AR)-2,9-BIS(6-AMINO-9H-PURIN-9-YL)OCTAHYDRO-2H,7H-DIFURO[3,2-D 3,2-J][1,3,7,9,2,8]TETRAOXADIPHOSPHACYCLODODECINE-3,5,10,12-TETROL+5,12-DIOXIDE'>2BA</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.25&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3c1y|3c1y]], [[3c1z|3c1z]], [[3c21|3c21]], [[3c23|3c23]], [[4yvz|4yvz]], [[4yxj|4yxj]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2BA:(2R,3R,3AS,5R,7AR,9R,10R,10AS,12R,14AR)-2,9-BIS(6-AMINO-9H-PURIN-9-YL)OCTAHYDRO-2H,7H-DIFURO[3,2-D 3,2-J][1,3,7,9,2,8]TETRAOXADIPHOSPHACYCLODODECINE-3,5,10,12-TETROL+5,12-DIOXIDE'>2BA</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Diadenylate_cyclase Diadenylate cyclase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.85 2.7.7.85] </span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4yxm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yxm OCA], [https://pdbe.org/4yxm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yxm RCSB], [https://www.ebi.ac.uk/pdbsum/4yxm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yxm ProSAT]</span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4yxm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yxm OCA], [http://pdbe.org/4yxm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4yxm RCSB], [http://www.ebi.ac.uk/pdbsum/4yxm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4yxm ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/DISA_THEMA DISA_THEMA]] Participates in a DNA-damage check-point. DisA forms globular foci that rapidly scan along the chromosomes searching for lesions (By similarity).<ref>PMID:18439896</ref>   Has also diadenylate cyclase activity, catalyzing the condensation of 2 ATP molecules into cyclic di-AMP (c-di-AMP). c-di-AMP likely acts as a signaling molecule that may couple DNA integrity with a cellular process. Does not convert GTP to c-di-GMP.<ref>PMID:18439896</ref>
+[https://www.uniprot.org/uniprot/DISA_THEMA DISA_THEMA] Participates in a DNA-damage check-point. DisA forms globular foci that rapidly scan along the chromosomes searching for lesions (By similarity).<ref>PMID:18439896</ref>   Has also diadenylate cyclase activity, catalyzing the condensation of 2 ATP molecules into cyclic di-AMP (c-di-AMP). c-di-AMP likely acts as a signaling molecule that may couple DNA integrity with a cellular process. Does not convert GTP to c-di-GMP.<ref>PMID:18439896</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 24: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Diadenylate cyclase]]
+[[Category: Large Structures]]
-[[Category: Deimling, T]]
+[[Category: Thermotoga maritima]]
-[[Category: Hopfner, K P]]
+[[Category: Deimling T]]
-[[Category: Mueller, M]]
+[[Category: Hopfner K-P]]
-[[Category: Witte, G]]
+[[Category: Mueller M]]
-[[Category: C-di-amp synthesis]]
+[[Category: Witte G]]
-[[Category: Dac domain]]
-[[Category: Dna binding protein]]
-[[Category: Inhibitor]]
-[[Category: Pre-reaction state]]
-[[Category: Transferase]]

4yxm

From Proteopedia

Current revision

Structure of Thermotoga maritima DisA D75N mutant with reaction product c-di-AMP

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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