1zot

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[[Image:1zot.gif|left|200px]]<br /><applet load="1zot" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1zot, resolution 2.20&Aring;" />
 
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'''crystal structure analysis of the CyaA/C-Cam with PMEAPP'''<br />
 
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==Overview==
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==crystal structure analysis of the CyaA/C-Cam with PMEAPP==
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CyaA is crucial for colonization by Bordetella pertussis, the etiologic agent of whooping cough. Here we report crystal structures of the adenylyl cyclase domain (ACD) of CyaA with the C-terminal domain of calmodulin. Four discrete regions of CyaA bind calcium-loaded calmodulin with a large buried contact surface. Of those, a tryptophan residue (W242) at an alpha-helix of CyaA makes extensive contacts with the calcium-induced, hydrophobic pocket of calmodulin. Mutagenic analyses show that all four regions of CyaA contribute to calmodulin binding and the calmodulin-induced conformational change of CyaA is crucial for catalytic activation. A crystal structure of CyaA-calmodulin with adefovir diphosphate, the metabolite of an approved antiviral drug, reveals the location of catalytic site of CyaA and how adefovir diphosphate tightly binds CyaA. The ACD of CyaA shares a similar structure and mechanism of activation with anthrax edema factor (EF). However, the interactions of CyaA with calmodulin completely diverge from those of EF. This provides molecular details of how two structurally homologous bacterial toxins evolved divergently to bind calmodulin, an evolutionarily conserved calcium sensor.
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<StructureSection load='1zot' size='340' side='right'caption='[[1zot]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1zot]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bordetella_pertussis Bordetella pertussis] 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=1ZOT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZOT FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
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<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=EMA:(ADENIN-9-YL-ETHOXYMETHYL)-HYDROXYPHOSPHINYL-DIPHOSPHATE'>EMA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1zot FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zot OCA], [https://pdbe.org/1zot PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zot RCSB], [https://www.ebi.ac.uk/pdbsum/1zot PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zot ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/CYAA_BORPE CYAA_BORPE] This adenylate cyclase belongs to a special class of bacterial toxin. It causes whooping cough by acting on mammalian cells by elevating cAMP-concentration and thus disrupts normal cell function.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zo/1zot_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1zot ConSurf].
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<div style="clear:both"></div>
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==Disease==
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==See Also==
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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]]
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*[[Calmodulin 3D structures|Calmodulin 3D structures]]
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*[[3D Adenylyl cyclase 3D structures|3D Adenylyl cyclase 3D structures]]
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==About this Structure==
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__TOC__
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1ZOT is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Bordetella_pertussis Bordetella pertussis] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CA:'>CA</scene>, <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=EMA:'>EMA</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=1ZOT OCA].
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</StructureSection>
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==Reference==
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Structural basis for the interaction of Bordetella pertussis adenylyl cyclase toxin with calmodulin., Guo Q, Shen Y, Lee YS, Gibbs CS, Mrksich M, Tang WJ, EMBO J. 2005 Sep 21;24(18):3190-201. Epub 2005 Sep 1. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16138079 16138079]
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[[Category: Adenylate cyclase]]
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[[Category: Bordetella pertussis]]
[[Category: Bordetella pertussis]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Protein complex]]
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[[Category: Large Structures]]
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[[Category: Guo, Q.]]
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[[Category: Guo Q]]
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[[Category: Tang, W J.]]
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[[Category: Tang WJ]]
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[[Category: CA]]
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[[Category: EMA]]
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[[Category: MG]]
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[[Category: adenylyl cyclase toxin]]
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[[Category: atp]]
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[[Category: calmodulin-binding]]
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[[Category: cyaa]]
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[[Category: pmeapp]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:17:39 2008''
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Current revision

crystal structure analysis of the CyaA/C-Cam with PMEAPP

PDB ID 1zot

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