1xfv

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[[Image:1xfv.gif|left|200px]]
 
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{{Structure
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==Crystal structure of anthrax edema factor (EF) in complex with calmodulin and 3' deoxy-ATP==
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|PDB= 1xfv |SIZE=350|CAPTION= <scene name='initialview01'>1xfv</scene>, resolution 3.35&Aring;
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<StructureSection load='1xfv' size='340' side='right'caption='[[1xfv]], [[Resolution|resolution]] 3.35&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene> and <scene name='pdbligand=3AT:3&#39;-DEOXYADENOSINE-5&#39;-TRIPHOSPHATE'>3AT</scene>
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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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|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]
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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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|GENE= cya ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1392 Bacillus anthracis])
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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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}}
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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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'''Crystal structure of anthrax edema factor (EF) in complex with calmodulin and 3' deoxy-ATP'''
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==See Also==
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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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==Overview==
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__TOC__
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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>
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==Disease==
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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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==About this Structure==
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1XFV 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]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XFV OCA].
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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://www.ncbi.nlm.nih.gov/pubmed/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 interaction]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 23 14:12:54 2008''
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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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