1j7n

From Proteopedia

(Difference between revisions)

Revision as of 10:31, 25 December 2014

Anthrax 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.
Ligands:	,
Gene:	lef (Bacillus anthracis)
Resources:	FirstGlance, OCA, RCSB, PDBsum

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]

Publication Abstract from PubMed

Lethal factor (LF) is a protein (relative molecular mass 90,000) that is critical in the pathogenesis of anthrax. It is a highly specific protease that cleaves members of the mitogen-activated protein kinase kinase (MAPKK) family near to their amino termini, leading to the inhibition of one or more signalling pathways. Here we describe the crystal structure of LF and its complex with the N terminus of MAPKK-2. LF comprises four domains: domain I binds the membrane-translocating component of anthrax toxin, the protective antigen (PA); domains II, III and IV together create a long deep groove that holds the 16-residue N-terminal tail of MAPKK-2 before cleavage. Domain II resembles the ADP-ribosylating toxin from Bacillus cereus, but the active site has been mutated and recruited to augment substrate recognition. Domain III is inserted into domain II, and seems to have arisen from a repeated duplication of a structural element of domain II. Domain IV is distantly related to the zinc metalloprotease family, and contains the catalytic centre; it also resembles domain I. The structure thus reveals a protein that has evolved through a process of gene duplication, mutation and fusion, into an enzyme with high and unusual specificity.

Crystal structure of the anthrax lethal factor.,Pannifer AD, Wong TY, Schwarzenbacher R, Renatus M, Petosa C, Bienkowska J, Lacy DB, Collier RJ, Park S, Leppla SH, Hanna P, Liddington RC Nature. 2001 Nov 8;414(6860):229-33. PMID:11700563^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ Pannifer AD, Wong TY, Schwarzenbacher R, Renatus M, Petosa C, Bienkowska J, Lacy DB, Collier RJ, Park S, Leppla SH, Hanna P, Liddington RC. Crystal structure of the anthrax lethal factor. Nature. 2001 Nov 8;414(6860):229-33. PMID:11700563 doi:10.1038/n35101998

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1j7n"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[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]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1J7N FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">lef ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1392 Bacillus anthracis])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">lef ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1392 Bacillus anthracis])</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=1j7n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1j7n OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1j7n RCSB], [http://www.ebi.ac.uk/pdbsum/1j7n PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1j7n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1j7n OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1j7n RCSB], [http://www.ebi.ac.uk/pdbsum/1j7n PDBsum]</span></td></tr>
-<table>
+</table>
+== Function ==
+[[http://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>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 25: @@
 </StructureSection>
 [[Category: Bacillus anthracis]]
-[[Category: Bienkowska, J.]]
+[[Category: Bienkowska, J]]
-[[Category: Collier, R J.]]
+[[Category: Collier, R J]]
-[[Category: Hanna, P.]]
+[[Category: Hanna, P]]
-[[Category: Lacy, D B.]]
+[[Category: Lacy, D B]]
-[[Category: Leppla, S H.]]
+[[Category: Leppla, S H]]
-[[Category: Liddington, R C.]]
+[[Category: Liddington, R C]]
-[[Category: Pannifer, A D.]]
+[[Category: Pannifer, A D]]
-[[Category: Park, S.]]
+[[Category: Park, S]]
-[[Category: Petosa, C.]]
+[[Category: Petosa, C]]
-[[Category: Renatus, M.]]
+[[Category: Renatus, M]]
-[[Category: Schwarzenbacher, R.]]
+[[Category: Schwarzenbacher, R]]
-[[Category: Wong, T Y.]]
+[[Category: Wong, T Y]]
 [[Category: Anthrax]]
 [[Category: Lethal factor]]

1j7n

From Proteopedia

Revision as of 10:31, 25 December 2014

Anthrax Toxin Lethal factor

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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