View source for 1jky


==Crystal Structure of the Anthrax Lethal Factor (LF): Wild-type LF Complexed with the N-terminal Sequence of MAPKK2==
<StructureSection load='1jky' size='340' side='right'caption='[[1jky]], [[Resolution|resolution]] 3.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1jky]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_anthracis Bacillus anthracis] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. 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=1JKY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1JKY 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]] 3.9&#8491;</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=1jky FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jky OCA], [https://pdbe.org/1jky PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1jky RCSB], [https://www.ebi.ac.uk/pdbsum/1jky PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1jky 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> 
<div style="background-color:#fffaf0;">
== 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<ref>PMID:11700563</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1jky" style="background-color:#fffaf0;"></div>

==See Also==
*[[Anthrax lethal factor 3D structures|Anthrax lethal factor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Anthrax Toxin]]
[[Category: Bacillus anthracis]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: Bienkowska J]]
[[Category: Collier RJ]]
[[Category: Hanna P]]
[[Category: Lacy DB]]
[[Category: Leppla SH]]
[[Category: Liddington RC]]
[[Category: Pannifer AD]]
[[Category: Park S]]
[[Category: Petosa C]]
[[Category: Renatus M]]
[[Category: Schwarzenbacher R]]
[[Category: Wong TY]]