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| | <StructureSection load='4yvz' size='340' side='right'caption='[[4yvz]], [[Resolution|resolution]] 2.50Å' scene=''> | | <StructureSection load='4yvz' size='340' side='right'caption='[[4yvz]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4yvz]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_43589 Atcc 43589]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YVZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YVZ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4yvz]] 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=4YVZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YVZ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3AT:3-DEOXYADENOSINE-5-TRIPHOSPHATE'>3AT</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3AT:3-DEOXYADENOSINE-5-TRIPHOSPHATE'>3AT</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></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]]</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=4yvz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yvz OCA], [https://pdbe.org/4yvz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yvz RCSB], [https://www.ebi.ac.uk/pdbsum/4yvz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yvz ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">disA, TM_0200 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=2336 ATCC 43589])</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4yvz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yvz OCA], [http://pdbe.org/4yvz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4yvz RCSB], [http://www.ebi.ac.uk/pdbsum/4yvz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4yvz ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == 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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Atcc 43589]] | |
| - | [[Category: Diadenylate cyclase]] | |
| | [[Category: Large Structures]] | | [[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]]
| + | |
| Structural highlights
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
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