|
|
| Line 1: |
Line 1: |
| | | | |
| | ==Characterization of an essential diadenylate cyclase== | | ==Characterization of an essential diadenylate cyclase== |
| - | <StructureSection load='4rv7' size='340' side='right' caption='[[4rv7]], [[Resolution|resolution]] 2.80Å' scene=''> | + | <StructureSection load='4rv7' size='340' side='right'caption='[[4rv7]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4rv7]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Lismo Lismo]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RV7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RV7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4rv7]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Listeria_monocytogenes_EGD-e Listeria monocytogenes EGD-e]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RV7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RV7 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=HEZ:HEXANE-1,6-DIOL'>HEZ</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=HEZ:HEXANE-1,6-DIOL'>HEZ</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">dacA, lmo2120 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=169963 LISMO])</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=4rv7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rv7 OCA], [https://pdbe.org/4rv7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rv7 RCSB], [https://www.ebi.ac.uk/pdbsum/4rv7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rv7 ProSAT]</span></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=4rv7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rv7 OCA], [http://pdbe.org/4rv7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rv7 RCSB], [http://www.ebi.ac.uk/pdbsum/4rv7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rv7 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DACA_LISMO DACA_LISMO]] Catalyzes the condensation of 2 ATP molecules into cyclic di-AMP (c-di-AMP), a signaling compound secreted into the host's cytosol where it triggers the cytosolic surveillance pathway (CSP), a host pathway of innate immunity characterized by expression of beta interferon (IFN-beta) and coregulated genes.<ref>PMID:20508090</ref> | + | [https://www.uniprot.org/uniprot/DACA_LISMO DACA_LISMO] Catalyzes the condensation of 2 ATP molecules into cyclic di-AMP (c-di-AMP), a signaling compound secreted into the host's cytosol where it triggers the cytosolic surveillance pathway (CSP), a host pathway of innate immunity characterized by expression of beta interferon (IFN-beta) and coregulated genes.<ref>PMID:20508090</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 24: |
Line 22: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Diadenylate cyclase]] | + | [[Category: Large Structures]] |
| - | [[Category: Lismo]] | + | [[Category: Listeria monocytogenes EGD-e]] |
| - | [[Category: Dickmanns, A]] | + | [[Category: Dickmanns A]] |
| - | [[Category: Ficner, R]] | + | [[Category: Ficner R]] |
| - | [[Category: Neumann, P]] | + | [[Category: Neumann P]] |
| - | [[Category: Atp binding]]
| + | |
| - | [[Category: C-di-amp binding]]
| + | |
| - | [[Category: Dac-fold]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
DACA_LISMO Catalyzes the condensation of 2 ATP molecules into cyclic di-AMP (c-di-AMP), a signaling compound secreted into the host's cytosol where it triggers the cytosolic surveillance pathway (CSP), a host pathway of innate immunity characterized by expression of beta interferon (IFN-beta) and coregulated genes.[1]
Publication Abstract from PubMed
The recently identified second messenger cyclic di-AMP (c-di-AMP) is involved in several important cellular processes, such as cell wall metabolism, maintenance of DNA integrity, ion transport, transcription regulation, and allosteric regulation of enzyme function. Interestingly, c-di-AMP is essential for growth of the Gram-positive model bacterium Bacillus subtilis. Although the genome of B. subtilis encodes three c-di-AMP-producing diadenlyate cyclases that can functionally replace each other, the phylogenetically related human pathogens like Listeria monocytogenes and Staphylococcus aureus possess only one enzyme, the diadenlyate cyclase CdaA. Because CdaA is also essential for growth of these bacteria, the enzyme is a promising target for the development of novel antibiotics. Here we present the first crystal structure of the L. monocytogenes CdaA diadenylate cyclase domain that is conserved in many human pathogens. Moreover, biochemical characterization of the cyclase revealed an unusual metal cofactor requirement.
Structural and Biochemical Analysis of the Essential Diadenylate Cyclase CdaA from Listeria monocytogenes.,Rosenberg J, Dickmanns A, Neumann P, Gunka K, Arens J, Kaever V, Stulke J, Ficner R, Commichau FM J Biol Chem. 2015 Mar 6;290(10):6596-606. doi: 10.1074/jbc.M114.630418. Epub 2015, Jan 20. PMID:25605729[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Woodward JJ, Iavarone AT, Portnoy DA. c-di-AMP secreted by intracellular Listeria monocytogenes activates a host type I interferon response. Science. 2010 Jun 25;328(5986):1703-5. doi: 10.1126/science.1189801. Epub 2010, May 27. PMID:20508090 doi:http://dx.doi.org/10.1126/science.1189801
- ↑ Rosenberg J, Dickmanns A, Neumann P, Gunka K, Arens J, Kaever V, Stulke J, Ficner R, Commichau FM. Structural and Biochemical Analysis of the Essential Diadenylate Cyclase CdaA from Listeria monocytogenes. J Biol Chem. 2015 Mar 6;290(10):6596-606. doi: 10.1074/jbc.M114.630418. Epub 2015, Jan 20. PMID:25605729 doi:http://dx.doi.org/10.1074/jbc.M114.630418
|
