1pk0

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(New page: 200px<br /> <applet load="1pk0" size="450" color="white" frame="true" align="right" spinBox="true" caption="1pk0, resolution 3.30&Aring;" /> '''Crystal Structure o...)
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[[Image:1pk0.gif|left|200px]]<br />
 
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<applet load="1pk0" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1pk0, resolution 3.30&Aring;" />
 
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'''Crystal Structure of the EF3-CaM complexed with PMEApp'''<br />
 
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==Overview==
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==Crystal Structure of the EF3-CaM complexed with PMEApp==
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Edema factor (EF), a key virulence factor in anthrax pathogenesis, has, calmodulin (CaM)-activated adenylyl cyclase activity. We have found that, adefovir dipivoxil, a drug approved to treat chronic infection of, hepatitis B virus, effectively inhibits EF-induced cAMP accumulation and, changes in cytokine production in mouse primary macrophages. Adefovir, diphosphate (PMEApp), the active cellular metabolite of adefovir, dipivoxil, inhibits the adenylyl cyclase activity of EF in vitro with high, affinity (K(i) = 27 nM). A crystal structure of EF-CaM-PMEApp reveals that, the catalytic site of EF forms better van der Waals contacts and more, hydrogen bonds with PMEApp than with its endogenous substrate, ATP, providing an explanation for the approximately 10,000-fold higher affinity, EF-CaM has for PMEApp versus ATP. Adefovir dipivoxil is a clinically, approved drug that can block the action of an anthrax toxin. It can be, used to address the role of EF in anthrax pathogenesis.
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<StructureSection load='1pk0' size='340' side='right'caption='[[1pk0]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1pk0]] 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=1PK0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PK0 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]] 3.3&#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=YB:YTTERBIUM+(III)+ION'>YB</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=1pk0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pk0 OCA], [https://pdbe.org/1pk0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pk0 RCSB], [https://www.ebi.ac.uk/pdbsum/1pk0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pk0 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/pk/1pk0_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=1pk0 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|Anthrax edema factor]]
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*[[Anthrax edema factor 3D structures|Anthrax edema factor 3D structures]]
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==About this Structure==
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*[[Calmodulin 3D structures|Calmodulin 3D structures]]
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1PK0 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, YB and EMA 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=1PK0 OCA].
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__TOC__
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</StructureSection>
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==Reference==
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Selective inhibition of anthrax edema factor by adefovir, a drug for chronic hepatitis B virus infection., Shen Y, Zhukovskaya NL, Zimmer MI, Soelaiman S, Bergson P, Wang CR, Gibbs CS, Tang WJ, Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):3242-7. Epub 2004 Feb 20. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=14978283 14978283]
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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: Shen, Y.]]
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[[Category: Shen Y]]
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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: YB]]
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[[Category: cam]]
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[[Category: edema factor]]
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[[Category: prodrug complex]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 18:43:57 2007''
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Current revision

Crystal Structure of the EF3-CaM complexed with PMEApp

PDB ID 1pk0

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