1lvc: Difference between revisions

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-[[Image:1lvc.jpg|left|200px]]<br /><applet load="1lvc" size="350" color="white" frame="true" align="right" spinBox="true"
-caption="1lvc, resolution 3.60&Aring;" />
-'''Crystal structure of the adenylyl cyclase domain of anthrax edema factor (EF) in complex with calmodulin and 2' deoxy, 3' anthraniloyl ATP'''<br />
-==Overview==
+==Crystal structure of the adenylyl cyclase domain of anthrax edema factor (EF) in complex with calmodulin and 2' deoxy, 3' anthraniloyl ATP==
-Edema factor (EF) and CyaA are calmodulin (CaM)-activated adenylyl cyclase, exotoxins involved in the pathogenesis of anthrax and whooping cough, respectively. Using spectroscopic, enzyme kinetic and surface plasmon, resonance spectroscopy analyses, we show that low Ca(2+) concentrations, increase the affinity of CaM for EF and CyaA causing their activation, but, higher Ca(2+) concentrations directly inhibit catalysis. Both events occur, in a physiologically relevant range of Ca(2+) concentrations. Despite the, similarity in Ca(2+) sensitivity, EF and CyaA have substantial differences, in CaM binding and activation. CyaA has 100-fold higher affinity for CaM, than EF. CaM has N- and C-terminal globular domains, each binding two, Ca(2+) ions. CyaA can be fully activated by CaM mutants with one defective, C-terminal Ca(2+)-binding site or by either terminal domain of CaM while, EF cannot. EF consists of a catalytic core and a helical domain, and both, are required for CaM activation of EF. Mutations that decrease the, interaction of the helical domain with the catalytic core create an enzyme, with higher sensitivity to Ca(2+)-CaM activation. However, CyaA is fully, activated by CaM without the domain corresponding to the helical domain of, EF.
+<StructureSection load='1lvc' size='340' side='right'caption='[[1lvc]], [[Resolution|resolution]] 3.60&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1lvc]] 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]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LVC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LVC FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.6&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DOT:3ANTHRANILOYL-2-DEOXY-ADENOSINE-5-TRIPHOSPHATE'>DOT</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=1lvc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lvc OCA], [https://pdbe.org/1lvc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1lvc RCSB], [https://www.ebi.ac.uk/pdbsum/1lvc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1lvc ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/CYAA_BACAN CYAA_BACAN] One of the three proteins composing the anthrax toxin, the agent which infects many mammalian species and that may cause death. EF is a calmodulin-dependent adenylyl cyclase that, when associated with PA, causes edema. EF is not toxic by itself and it is required for the survival of germinated spores within macrophages at the early stages of infection. Provokes dramatic elevation of intracellular cAMP levels in the host.
+== 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/lv/1lvc_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=1lvc ConSurf].
+<div style="clear:both"></div>
-==Disease==
+==See Also==
-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]]
+*[[Anthrax edema factor 3D structures|Anthrax edema factor 3D structures]]
+*[[Calmodulin 3D structures|Calmodulin 3D structures]]
-==About this Structure==
+__TOC__
-LVC is a [http://en.wikipedia.org/wiki/Protein_complex 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] with <scene name='pdbligand=CA:'>CA</scene>, <scene name='pdbligand=YB:'>YB</scene> and <scene name='pdbligand=DOT:'>DOT</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LVC OCA].
+</StructureSection>
-==Reference==
-Physiological calcium concentrations regulate calmodulin binding and catalysis of adenylyl cyclase exotoxins., Shen Y, Lee YS, Soelaiman S, Bergson P, Lu D, Chen A, Beckingham K, Grabarek Z, Mrksich M, Tang WJ, EMBO J. 2002 Dec 16;21(24):6721-32. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12485993 12485993]
-[[Category: Adenylate cyclase]]
 [[Category: Bacillus anthracis]]
 [[Category: Homo sapiens]]
-[[Category: Protein complex]]
+[[Category: Large Structures]]
-[[Category: Beckingham, K.]]
+[[Category: Beckingham K]]
-[[Category: Bergson, P.]]
+[[Category: Bergson P]]
-[[Category: Chen, A.]]
+[[Category: Chen A]]
-[[Category: Grabarek, Z.]]
+[[Category: Grabarek Z]]
-[[Category: Lee, Y.S.]]
+[[Category: Lee Y-S]]
-[[Category: Lu, D.]]
+[[Category: Lu D]]
-[[Category: Mrksich, M.]]
+[[Category: Mrksich M]]
-[[Category: Shen, Y.]]
+[[Category: Shen Y]]
-[[Category: Soelaiman, S.]]
+[[Category: Soelaiman S]]
-[[Category: Tang, W.J.]]
+[[Category: Tang W-J]]
-[[Category: CA]]
-[[Category: DOT]]
-[[Category: YB]]
-[[Category: helical domain]]
-[[Category: protein-protein complex]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:20:48 2008''