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==Crystal structure of the adenylyl cyclase domain of anthrax edema factor (EF)==
==Crystal structure of the adenylyl cyclase domain of anthrax edema factor (EF)==
<StructureSection load='1k8t' size='340' side='right' caption='[[1k8t]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
<StructureSection load='1k8t' size='340' side='right'caption='[[1k8t]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1k8t]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Bacillus_anthracis Bacillus anthracis]. The April 2002 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Anthrax Toxin''  by David S. Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2002_4 10.2210/rcsb_pdb/mom_2002_4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1K8T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1K8T FirstGlance]. <br>
<table><tr><td colspan='2'>[[1k8t]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_anthracis Bacillus anthracis]. The April 2002 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Anthrax Toxin''  by David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2002_4 10.2210/rcsb_pdb/mom_2002_4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1K8T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1K8T FirstGlance]. <br>
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><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]] 2.6&#8491;</td></tr>
<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1k8t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1k8t OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1k8t RCSB], [http://www.ebi.ac.uk/pdbsum/1k8t PDBsum]</span></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=1k8t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1k8t OCA], [https://pdbe.org/1k8t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1k8t RCSB], [https://www.ebi.ac.uk/pdbsum/1k8t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1k8t ProSAT]</span></td></tr>
<table>
</table>
<div style="background-color:#fffaf0;">
== Function ==
== Publication Abstract from PubMed ==
[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.
Oedema factor, a calmodulin-activated adenylyl cyclase, is important in the pathogenesis of anthrax. Here we report the X-ray structures of oedema factor with and without bound calmodulin. Oedema factor shares no significant structural homology with mammalian adenylyl cyclases or other proteins. In the active site, 3'-deoxy-ATP and a single metal ion are well positioned for catalysis with histidine 351 as the catalytic base. This mechanism differs from the mechanism of two-metal-ion catalysis proposed for mammalian adenylyl cyclases. Four discrete regions of oedema factor form a surface that recognizes an extended conformation of calmodulin, which is very different from the collapsed conformation observed in other structures of calmodulin bound to effector peptides. On calmodulin binding, an oedema factor helical domain of relative molecular mass 15,000 undergoes a 15 A translation and a 30 degrees rotation away from the oedema factor catalytic core, which stabilizes a disordered loop and leads to enzyme activation. These allosteric changes provide the first molecular details of how calmodulin modulates one of its targets.
 
Structural basis for the activation of anthrax adenylyl cyclase exotoxin by calmodulin.,Drum CL, Yan SZ, Bard J, Shen YQ, Lu D, Soelaiman S, Grabarek Z, Bohm A, Tang WJ Nature. 2002 Jan 24;415(6870):396-402. PMID:11807546<ref>PMID:11807546</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>


==See Also==
==See Also==
*[[Adenylyl cyclase|Adenylyl cyclase]]
*[[Anthrax edema factor 3D structures|Anthrax edema factor 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Adenylate cyclase]]
[[Category: Anthrax Toxin]]
[[Category: Anthrax Toxin]]
[[Category: Bacillus anthracis]]
[[Category: Bacillus anthracis]]
[[Category: Large Structures]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: Bard, J.]]
[[Category: Bard J]]
[[Category: Bohm, A.]]
[[Category: Bohm A]]
[[Category: Drum, C L.]]
[[Category: Drum CL]]
[[Category: Grabarek, Z.]]
[[Category: Grabarek Z]]
[[Category: Lu, D.]]
[[Category: Lu D]]
[[Category: Shen, Y Q.]]
[[Category: Shen Y-Q]]
[[Category: Soelaiman, S.]]
[[Category: Soelaiman S]]
[[Category: Tang, W J.]]
[[Category: Tang W-J]]
[[Category: Yan, S Z.]]
[[Category: Yan S-Z]]
[[Category: Adenylyl cyclase]]
[[Category: Anthrax]]
[[Category: Calmodulin]]
[[Category: Edema factor]]
[[Category: Lyase]]
[[Category: Toxin]]

Latest revision as of 10:45, 7 February 2024

Crystal structure of the adenylyl cyclase domain of anthrax edema factor (EF)Crystal structure of the adenylyl cyclase domain of anthrax edema factor (EF)

Structural highlights

1k8t is a 1 chain structure with sequence from Bacillus anthracis. The April 2002 RCSB PDB Molecule of the Month feature on Anthrax Toxin by David S. Goodsell is 10.2210/rcsb_pdb/mom_2002_4. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.6Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.

See Also

1k8t, resolution 2.60Å

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