1xfv

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(New page: 200px<br /> <applet load="1xfv" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xfv, resolution 3.35&Aring;" /> '''Crystal structure o...)
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[[Image:1xfv.gif|left|200px]]<br />
 
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<applet load="1xfv" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1xfv, resolution 3.35&Aring;" />
 
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'''Crystal structure of anthrax edema factor (EF) in complex with calmodulin and 3' deoxy-ATP'''<br />
 
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==Overview==
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==Crystal structure of anthrax edema factor (EF) in complex with calmodulin and 3' deoxy-ATP==
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Edema factor (EF), a key anthrax exotoxin, has an anthrax protective, antigen-binding domain (PABD) and a calmodulin (CaM)-activated adenylyl, cyclase domain. Here, we report the crystal structures of CaM-bound EF, revealing the architecture of EF PABD. CaM has N- and C-terminal domains, and each domain can bind two calcium ions. Calcium binding induces the, conformational change of CaM from closed to open. Structures of the EF-CaM, complex show how EF locks the N-terminal domain of CaM into a closed, conformation regardless of its calcium-loading state. This represents a, mechanism of how CaM effector alters the calcium affinity of CaM and, uncouples the conformational change of CaM from calcium loading., Furthermore, structures of EF-CaM complexed with nucleotides show that EF, uses two-metal-ion catalysis, a prevalent mechanism in DNA and RNA, polymerases. A histidine (H351) further facilitates the catalysis of EF by, activating a water to deprotonate 3'OH of ATP. Mammalian adenylyl cyclases, share no structural similarity with EF and they also use two-metal-ion, catalysis, suggesting the catalytic mechanism-driven convergent evolution, of two structurally diverse adenylyl cyclases.
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<StructureSection load='1xfv' size='340' side='right'caption='[[1xfv]], [[Resolution|resolution]] 3.35&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1xfv]] is a 12 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=1XFV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XFV 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]] 3.35&#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=3AT:3-DEOXYADENOSINE-5-TRIPHOSPHATE'>3AT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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=1xfv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xfv OCA], [https://pdbe.org/1xfv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xfv RCSB], [https://www.ebi.ac.uk/pdbsum/1xfv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xfv ProSAT]</span></td></tr>
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</table>
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== Function ==
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[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.
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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/xf/1xfv_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=1xfv 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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*[[Anthrax edema factor 3D structures|Anthrax edema factor 3D structures]]
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*[[Calmodulin 3D structures|Calmodulin 3D structures]]
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==About this Structure==
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__TOC__
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1XFV 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 CA, MG and 3AT 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1XFV OCA].
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</StructureSection>
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==Reference==
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Calcium-independent calmodulin binding and two-metal-ion catalytic mechanism of anthrax edema factor., Shen Y, Zhukovskaya NL, Guo Q, Florian J, Tang WJ, EMBO J. 2005 Mar 9;24(5):929-41. Epub 2005 Feb 17. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15719022 15719022]
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[[Category: Adenylate cyclase]]
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[[Category: Bacillus anthracis]]
[[Category: Bacillus anthracis]]
[[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: Florian, J.]]
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[[Category: Florian J]]
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[[Category: Guo, Q.]]
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[[Category: Guo Q]]
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[[Category: Shen, Q.]]
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[[Category: Shen Q]]
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[[Category: Tang, W.J.]]
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[[Category: Tang WJ]]
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[[Category: Zhukovskaya, N.L.]]
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[[Category: Zhukovskaya NL]]
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[[Category: 3AT]]
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[[Category: CA]]
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[[Category: MG]]
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[[Category: protein-protein interactions]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 20:04:46 2007''
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Current revision

Crystal structure of anthrax edema factor (EF) in complex with calmodulin and 3' deoxy-ATP

PDB ID 1xfv

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