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| - | [[Image:1k90.gif|left|200px]] | |
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| - | {{Structure
| + | ==Crystal structure of the adenylyl cyclase domain of anthrax edema factor (EF) in complex with calmodulin and 3' deoxy-ATP== |
| - | |PDB= 1k90 |SIZE=350|CAPTION= <scene name='initialview01'>1k90</scene>, resolution 2.75Å
| + | <StructureSection load='1k90' size='340' side='right'caption='[[1k90]], [[Resolution|resolution]] 2.75Å' scene=''> |
| - | |SITE=
| + | == Structural highlights == |
| - | |LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=YB:YTTERBIUM+(III)+ION'>YB</scene> and <scene name='pdbligand=3AT:3'-DEOXYADENOSINE-5'-TRIPHOSPHATE'>3AT</scene> | + | <table><tr><td colspan='2'>[[1k90]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_anthracis Bacillus anthracis] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The April 2002 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Anthrax Toxin'' by David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2002_4 10.2210/rcsb_pdb/mom_2002_4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1K90 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1K90 FirstGlance]. <br> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Adenylate_cyclase Adenylate cyclase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.6.1.1 4.6.1.1]
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.75Å</td></tr> |
| - | |GENE= | + | <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=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=YB:YTTERBIUM+(III)+ION'>YB</scene></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=1k90 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1k90 OCA], [https://pdbe.org/1k90 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1k90 RCSB], [https://www.ebi.ac.uk/pdbsum/1k90 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1k90 ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Disease == |
| | + | [https://www.uniprot.org/uniprot/CALM1_HUMAN CALM1_HUMAN] The disease is caused by mutations affecting the gene represented in this entry. Mutations in CALM1 are the cause of CPVT4. The disease is caused by mutations affecting the gene represented in this entry. Mutations in CALM1 are the cause of LQT14. |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/CALM1_HUMAN CALM1_HUMAN] Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis (PubMed:16760425). Mediates calcium-dependent inactivation of CACNA1C (PubMed:26969752). Positively regulates calcium-activated potassium channel activity of KCNN2 (PubMed:27165696).<ref>PMID:16760425</ref> <ref>PMID:23893133</ref> <ref>PMID:26969752</ref> <ref>PMID:27165696</ref> |
| | + | == Evolutionary Conservation == |
| | + | [[Image:Consurf_key_small.gif|200px|right]] |
| | + | Check<jmol> |
| | + | <jmolCheckbox> |
| | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/k9/1k90_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | + | <text>to colour the structure by Evolutionary Conservation</text> |
| | + | </jmolCheckbox> |
| | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1k90 ConSurf]. |
| | + | <div style="clear:both"></div> |
| | | | |
| - | '''Crystal structure of the adenylyl cyclase domain of anthrax edema factor (EF) in complex with calmodulin and 3' deoxy-ATP'''
| + | ==See Also== |
| - | | + | *[[Anthrax edema factor 3D structures|Anthrax edema factor 3D structures]] |
| - | | + | *[[Calmodulin 3D structures|Calmodulin 3D structures]] |
| - | ==Overview== | + | == References == |
| - | Oedema factor, a calmodulin-activated adenylyl cyclase, is important in the pathogenesis of anthrax. Here we report the X-ray structures of oedema factor with and without bound calmodulin. Oedema factor shares no significant structural homology with mammalian adenylyl cyclases or other proteins. In the active site, 3'-deoxy-ATP and a single metal ion are well positioned for catalysis with histidine 351 as the catalytic base. This mechanism differs from the mechanism of two-metal-ion catalysis proposed for mammalian adenylyl cyclases. Four discrete regions of oedema factor form a surface that recognizes an extended conformation of calmodulin, which is very different from the collapsed conformation observed in other structures of calmodulin bound to effector peptides. On calmodulin binding, an oedema factor helical domain of relative molecular mass 15,000 undergoes a 15 A translation and a 30 degrees rotation away from the oedema factor catalytic core, which stabilizes a disordered loop and leads to enzyme activation. These allosteric changes provide the first molecular details of how calmodulin modulates one of its targets.
| + | <references/> |
| - | | + | __TOC__ |
| - | ==Disease==
| + | </StructureSection> |
| - | Known diseases associated with this structure: Cavernous malformations of CNS and retina OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=604214 604214]], Cerebral cavernous malformations-1 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=604214 604214]], Hyperkeratotic cutaneous capillary-venous malformations associated with cerebral capillary malformations OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=604214 604214]], Leukemia, acute T-cell lymphoblastic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=603025 603025]], Leukemia, acute myeloid OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=603025 603025]]
| + | |
| - | | + | |
| - | ==About this Structure== | + | |
| - | 1K90 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Bacillus_anthracis Bacillus anthracis] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The following page contains interesting information on the relation of 1K90 with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb28_1.html Anthrax Toxin]]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1K90 OCA].
| + | |
| - | | + | |
| - | ==Reference==
| + | |
| - | Structural basis for the activation of anthrax adenylyl cyclase exotoxin by calmodulin., Drum CL, Yan SZ, Bard J, Shen YQ, Lu D, Soelaiman S, Grabarek Z, Bohm A, Tang WJ, Nature. 2002 Jan 24;415(6870):396-402. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11807546 11807546]
| + | |
| - | [[Category: Adenylate cyclase]]
| + | |
| | [[Category: Anthrax Toxin]] | | [[Category: Anthrax Toxin]] |
| | [[Category: Bacillus anthracis]] | | [[Category: Bacillus anthracis]] |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Protein complex]] | + | [[Category: Large Structures]] |
| - | [[Category: Bard, J.]] | + | [[Category: RCSB PDB Molecule of the Month]] |
| - | [[Category: Bohm, A.]] | + | [[Category: Bard J]] |
| - | [[Category: Drum, C L.]] | + | [[Category: Bohm A]] |
| - | [[Category: Grabarek, Z.]] | + | [[Category: Drum CL]] |
| - | [[Category: Lu, D.]] | + | [[Category: Grabarek Z]] |
| - | [[Category: Shen, Y Q.]] | + | [[Category: Lu D]] |
| - | [[Category: Soelaiman, S.]] | + | [[Category: Shen Y-Q]] |
| - | [[Category: Tang, W J.]] | + | [[Category: Soelaiman S]] |
| - | [[Category: Yan, S Z.]] | + | [[Category: Tang W-J]] |
| - | [[Category: 3AT]]
| + | [[Category: Yan S-Z]] |
| - | [[Category: CA]]
| + | |
| - | [[Category: YB]]
| + | |
| - | [[Category: oedema factor adenylyl cyclase anthrax calmodulin]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:14:10 2008''
| + | |
| Structural highlights
Disease
CALM1_HUMAN The disease is caused by mutations affecting the gene represented in this entry. Mutations in CALM1 are the cause of CPVT4. The disease is caused by mutations affecting the gene represented in this entry. Mutations in CALM1 are the cause of LQT14.
Function
CALM1_HUMAN Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis (PubMed:16760425). Mediates calcium-dependent inactivation of CACNA1C (PubMed:26969752). Positively regulates calcium-activated potassium channel activity of KCNN2 (PubMed:27165696).[1] [2] [3] [4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
See Also
References
- ↑ Tsang WY, Spektor A, Luciano DJ, Indjeian VB, Chen Z, Salisbury JL, Sanchez I, Dynlacht BD. CP110 cooperates with two calcium-binding proteins to regulate cytokinesis and genome stability. Mol Biol Cell. 2006 Aug;17(8):3423-34. Epub 2006 Jun 7. PMID:16760425 doi:10.1091/mbc.E06-04-0371
- ↑ Reichow SL, Clemens DM, Freites JA, Nemeth-Cahalan KL, Heyden M, Tobias DJ, Hall JE, Gonen T. Allosteric mechanism of water-channel gating by Ca-calmodulin. Nat Struct Mol Biol. 2013 Jul 28. doi: 10.1038/nsmb.2630. PMID:23893133 doi:10.1038/nsmb.2630
- ↑ Boczek NJ, Gomez-Hurtado N, Ye D, Calvert ML, Tester DJ, Kryshtal D, Hwang HS, Johnson CN, Chazin WJ, Loporcaro CG, Shah M, Papez AL, Lau YR, Kanter R, Knollmann BC, Ackerman MJ. Spectrum and Prevalence of CALM1-, CALM2-, and CALM3-Encoded Calmodulin Variants in Long QT Syndrome and Functional Characterization of a Novel Long QT Syndrome-Associated Calmodulin Missense Variant, E141G. Circ Cardiovasc Genet. 2016 Apr;9(2):136-146. doi:, 10.1161/CIRCGENETICS.115.001323. Epub 2016 Mar 11. PMID:26969752 doi:http://dx.doi.org/10.1161/CIRCGENETICS.115.001323
- ↑ Yu CC, Ko JS, Ai T, Tsai WC, Chen Z, Rubart M, Vatta M, Everett TH 4th, George AL Jr, Chen PS. Arrhythmogenic calmodulin mutations impede activation of small-conductance calcium-activated potassium current. Heart Rhythm. 2016 Aug;13(8):1716-23. doi: 10.1016/j.hrthm.2016.05.009. Epub 2016, May 7. PMID:27165696 doi:http://dx.doi.org/10.1016/j.hrthm.2016.05.009
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