1pwv

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[[Image:1pwv.png|left|200px]]
 
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{{STRUCTURE_1pwv| PDB=1pwv | SCENE= }}
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==Crystal structure of Anthrax Lethal Factor wild-type protein complexed with an optimised peptide substrate.==
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<StructureSection load='1pwv' size='340' side='right'caption='[[1pwv]], [[Resolution|resolution]] 2.85&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1pwv]] is a 4 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=1PWV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PWV 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]] 2.85&#8491;</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=1pwv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pwv OCA], [https://pdbe.org/1pwv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pwv RCSB], [https://www.ebi.ac.uk/pdbsum/1pwv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pwv ProSAT]</span></td></tr>
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</table>
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== Function ==
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[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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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Recent events have created an urgent need for new therapeutic strategies to treat anthrax. We have applied a mixture-based peptide library approach to rapidly determine the optimal peptide substrate for the anthrax lethal factor (LF), a metalloproteinase with an important role in the pathogenesis of the disease. Using this approach we have identified peptide analogs that inhibit the enzyme in vitro and that protect cultured macrophages from LF-mediated cytolysis. The crystal structures of LF bound to an optimized peptide substrate and to peptide-based inhibitors provide a rationale for the observed selectivity and may be exploited in the design of future generations of LF inhibitors.
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===Crystal structure of Anthrax Lethal Factor wild-type protein complexed with an optimised peptide substrate.===
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The structural basis for substrate and inhibitor selectivity of the anthrax lethal factor.,Turk BE, Wong TY, Schwarzenbacher R, Jarrell ET, Leppla SH, Collier RJ, Liddington RC, Cantley LC Nat Struct Mol Biol. 2004 Jan;11(1):60-6. Epub 2003 Dec 29. PMID:14718924<ref>PMID:14718924</ref>
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{{ABSTRACT_PUBMED_14718924}}
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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==About this Structure==
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<div class="pdbe-citations 1pwv" style="background-color:#fffaf0;"></div>
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[[1pwv]] is a 4 chain structure of [[Anthrax Lethal Factor]] with sequence from [http://en.wikipedia.org/wiki/Bacillus_anthracis Bacillus anthracis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PWV OCA].
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==See Also==
==See Also==
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*[[Anthrax Lethal Factor|Anthrax Lethal Factor]]
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*[[Anthrax lethal factor 3D structures|Anthrax lethal factor 3D structures]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:014718924</ref><references group="xtra"/>
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__TOC__
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</StructureSection>
[[Category: Bacillus anthracis]]
[[Category: Bacillus anthracis]]
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[[Category: Liddington, R C.]]
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[[Category: Large Structures]]
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[[Category: Schwarzenbacher, R.]]
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[[Category: Liddington RC]]
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[[Category: Wong, T Y.]]
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[[Category: Schwarzenbacher R]]
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[[Category: Anthrax toxin]]
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[[Category: Wong TY]]
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[[Category: Hydrolase]]
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[[Category: Lethal factor]]
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[[Category: Optimised peptide substrate]]
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Current revision

Crystal structure of Anthrax Lethal Factor wild-type protein complexed with an optimised peptide substrate.

PDB ID 1pwv

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