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4xm8

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Revision as of 12:16, 6 November 2017

Anthrax toxin lethal factor with ligand-induced binding pocket

Structural highlights

4xm8 is a 1 chain structure with sequence from "bacillus_cereus_var._anthracis"_(cohn_1872)_smith_et_al._1946 "bacillus cereus var. anthracis" (cohn 1872) smith et al. 1946. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	4pkq, 4pkr, 4pks, 4pkt, 4pku, 4pkv, 4pkw, 4wf6, 1yqy, 4xm6, 4xm7
Gene:	lef, pXO1-107, BXA0172, GBAA_pXO1_0172 ("Bacillus cereus var. anthracis" (Cohn 1872) Smith et al. 1946)
Activity:	Hydrolase, with EC number 3.4.24.83
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]

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

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4xm8"

@@ Line 1: / Line 1: @@
 ==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. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XM8 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4xm8]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_cereus_var._anthracis"_(cohn_1872)_smith_et_al._1946 "bacillus cereus var. anthracis" (cohn 1872) smith et al. 1946]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XM8 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4pkq|4pkq]], [[4pkr|4pkr]], [[4pks|4pks]], [[4pkt|4pkt]], [[4pku|4pku]], [[4pkv|4pkv]], [[4pkw|4pkw]], [[4wf6|4wf6]], [[1yqy|1yqy]], [[4xm6|4xm6]], [[4xm7|4xm7]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">lef, pXO1-107, BXA0172, GBAA_pXO1_0172 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1392 "Bacillus cereus var. anthracis" (Cohn 1872) Smith et al. 1946])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Hydrolase Hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.83 3.4.24.83] </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=4xm8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xm8 OCA], [http://pdbe.org/4xm8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xm8 RCSB], [http://www.ebi.ac.uk/pdbsum/4xm8 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=4xm8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xm8 OCA], [http://pdbe.org/4xm8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xm8 RCSB], [http://www.ebi.ac.uk/pdbsum/4xm8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4xm8 ProSAT]</span></td></tr>
 </table>
 == Function ==

4xm8

From Proteopedia

Revision as of 12:16, 6 November 2017

Anthrax toxin lethal factor with ligand-induced binding pocket

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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Views

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