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[[Image:1j7n.png|left|200px]]


{{STRUCTURE_1j7n|  PDB=1j7n  |  SCENE=  }}
==Anthrax Toxin Lethal factor==
 
<StructureSection load='1j7n' size='340' side='right'caption='[[1j7n]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
===Anthrax Toxin Lethal factor===
== Structural highlights ==
 
<table><tr><td colspan='2'>[[1j7n]] is a 2 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=1J7N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1J7N FirstGlance]. <br>
{{ABSTRACT_PUBMED_11700563}}
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
 
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
==About this Structure==
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1j7n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1j7n OCA], [https://pdbe.org/1j7n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1j7n RCSB], [https://www.ebi.ac.uk/pdbsum/1j7n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1j7n ProSAT]</span></td></tr>
[[1j7n]] is a 2 chain structure 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=1J7N OCA].  
</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>


==See Also==
==See Also==
*[[Anthrax Lethal Factor|Anthrax Lethal Factor]]
*[[Anthrax Lethal Factor|Anthrax Lethal Factor]]
 
*[[Anthrax lethal factor 3D structures|Anthrax lethal factor 3D structures]]
==Reference==
== References ==
<ref group="xtra">PMID:011700563</ref><ref group="xtra">PMID:014718925</ref><references group="xtra"/>
<references/>
__TOC__
</StructureSection>
[[Category: Bacillus anthracis]]
[[Category: Bacillus anthracis]]
[[Category: Bienkowska, J.]]
[[Category: Large Structures]]
[[Category: Collier, R J.]]
[[Category: Bienkowska J]]
[[Category: Hanna, P.]]
[[Category: Collier RJ]]
[[Category: Lacy, D B.]]
[[Category: Hanna P]]
[[Category: Leppla, S H.]]
[[Category: Lacy DB]]
[[Category: Liddington, R C.]]
[[Category: Leppla SH]]
[[Category: Pannifer, A D.]]
[[Category: Liddington RC]]
[[Category: Park, S.]]
[[Category: Pannifer AD]]
[[Category: Petosa, C.]]
[[Category: Park S]]
[[Category: Renatus, M.]]
[[Category: Petosa C]]
[[Category: Schwarzenbacher, R.]]
[[Category: Renatus M]]
[[Category: Wong, T Y.]]
[[Category: Schwarzenbacher R]]
[[Category: Anthrax]]
[[Category: Wong TY]]
[[Category: Lethal factor]]
[[Category: Lethal toxin]]
[[Category: Mapkk]]
[[Category: Mek]]
[[Category: Toxin]]
[[Category: Zinc metalloprotease]]

Latest revision as of 10:37, 7 February 2024

Anthrax Toxin Lethal factorAnthrax Toxin Lethal factor

Structural highlights

1j7n is a 2 chain structure with sequence from Bacillus anthracis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.3Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.[1] [2] [3] [4] [5]

See Also

References

  1. ↑ Duesbery NS, Webb CP, Leppla SH, Gordon VM, Klimpel KR, Copeland TD, Ahn NG, Oskarsson MK, Fukasawa K, Paull KD, Vande Woude GF. Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factor. Science. 1998 May 1;280(5364):734-7. PMID:9563949
  2. ↑ Vitale G, Pellizzari R, Recchi C, Napolitani G, Mock M, Montecucco C. Anthrax lethal factor cleaves the N-terminus of MAPKKs and induces tyrosine/threonine phosphorylation of MAPKs in cultured macrophages. Biochem Biophys Res Commun. 1998 Jul 30;248(3):706-11. PMID:9703991 doi:http://dx.doi.org/S0006-291X(98)99040-4
  3. ↑ Duesbery NS, Vande Woude GF. Anthrax lethal factor causes proteolytic inactivation of mitogen-activated protein kinase kinase. J Appl Microbiol. 1999 Aug;87(2):289-93. PMID:10475971
  4. ↑ Vitale G, Bernardi L, Napolitani G, Mock M, Montecucco C. Susceptibility of mitogen-activated protein kinase kinase family members to proteolysis by anthrax lethal factor. Biochem J. 2000 Dec 15;352 Pt 3:739-45. PMID:11104681
  5. ↑ Tang G, Leppla SH. Proteasome activity is required for anthrax lethal toxin to kill macrophages. Infect Immun. 1999 Jun;67(6):3055-60. PMID:10338520

1j7n, resolution 2.30Å

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