View source for 4xm8


==Anthrax toxin lethal factor with ligand-induced binding pocket==
<StructureSection load='4xm8' size='340' side='right'caption='[[4xm8]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4xm8]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_anthracis Bacillus anthracis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XM8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XM8 FirstGlance]. <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]] 2.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=41T:N-HYDROXY-N~2~-{[3-(METHOXYMETHYL)PHENYL]SULFONYL}-N~2~-(2-METHYLPROPYL)-D-VALINAMIDE'>41T</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=4xm8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xm8 OCA], [https://pdbe.org/4xm8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xm8 RCSB], [https://www.ebi.ac.uk/pdbsum/4xm8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xm8 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/LEF_BACAN LEF_BACAN] One of the three proteins composing the anthrax toxin, the agent which infects many mammalian species and that may cause death. LF is the lethal factor that, when associated with PA, causes death. LF is not toxic by itself. It is a protease that cleaves the N-terminal of most dual specificity mitogen-activated protein kinase kinases (MAPKKs or MAP2Ks) (except for MAP2K5). Cleavage invariably occurs within the N-terminal proline-rich region preceding the kinase domain, thus disrupting a sequence involved in directing specific protein-protein interactions necessary for the assembly of signaling complexes. There may be other cytosolic targets of LF involved in cytotoxicity. The proteasome may mediate a toxic process initiated by LF in the cell cytosol involving degradation of unidentified molecules that are essential for macrophage homeostasis. This is an early step in LeTx intoxication, but it is downstream of the cleavage by LF of MEK1 or other putative substrates.<ref>PMID:9563949</ref> <ref>PMID:9703991</ref> <ref>PMID:10475971</ref> <ref>PMID:11104681</ref> <ref>PMID:10338520</ref> 
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== Publication Abstract from PubMed ==
The Bacillus anthracis lethal factor (LF) is one component of a tripartite exotoxin partly responsible for persistent anthrax cytotoxicity after initial bacterial infection. Inhibitors of the zinc metalloproteinase have been investigated as potential therapeutic agents, but LF is a challenging target because inhibitors lack sufficient selectivity or possess poor pharmaceutical properties. These structural studies reveal an alternate conformation of the enzyme, induced upon binding of specific inhibitors, that opens a previously unobserved deep pocket termed S1' * which might afford new opportunities to design selective inhibitors that target this subsite.

Ligand-induced expansion of the S1' site in the anthrax toxin lethal factor.,Maize KM, Kurbanov EK, Johnson RL, Amin EA, Finzel BC FEBS Lett. 2015 Nov 11. pii: S0014-5793(15)00976-X. doi:, 10.1016/j.febslet.2015.11.005. PMID:26578066<ref>PMID:26578066</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4xm8" style="background-color:#fffaf0;"></div>

==See Also==
*[[Anthrax lethal factor 3D structures|Anthrax lethal factor 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Bacillus anthracis]]
[[Category: Large Structures]]
[[Category: Finzel BC]]
[[Category: Maize KM]]