1ikp

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
(New page: 200px<br /><applet load="1ikp" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ikp, resolution 1.45&Aring;" /> '''Pseudomonas Aerugino...)
Current revision (06:02, 3 April 2024) (edit) (undo)
 
(16 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:1ikp.jpg|left|200px]]<br /><applet load="1ikp" size="450" color="white" frame="true" align="right" spinBox="true"
 
-
caption="1ikp, resolution 1.45&Aring;" />
 
-
'''Pseudomonas Aeruginosa Exotoxin A, P201Q, W281A mutant'''<br />
 
-
==Overview==
+
==Pseudomonas Aeruginosa Exotoxin A, P201Q, W281A mutant==
-
Exotoxin A of Pseudomonas aeruginosa asserts its cellular toxicity through, ADP-ribosylation of translation elongation factor 2, predicated on binding, to specific cell surface receptors and intracellular trafficking via a, complex pathway that ultimately results in translocation of an enzymatic, activity into the cytoplasm. In early work, the crystallographic structure, of exotoxin A was determined to 3.0 A resolution, revealing a tertiary, fold having three distinct structural domains; subsequent work has shown, that the domains are individually responsible for the receptor binding, (domain I), transmembrane targeting (domain II), and ADP-ribosyl, transferase (domain III) activities, respectively. Here, we report the, structures of wild-type and W281A mutant toxin proteins at pH 8.0, refined, with data to 1.62 A and 1.45 A resolution, respectively. The refined, models clarify several ionic interactions within structural domains I and, II that may modulate an obligatory conformational change that is induced, by low pH. Proteolytic cleavage by furin is also obligatory for toxicity;, the W281A mutant protein is substantially more susceptible to cleavage, than the wild-type toxin. The tertiary structures of the furin cleavage, sites of the wild-type and W281 mutant toxins are similar; however, the, mutant toxin has significantly higher B-factors around the cleavage site, suggesting that the greater susceptibility to furin cleavage is due to, increased local disorder/flexibility at the site, rather than to, differences in static tertiary structure. Comparison of the refined, structures of full-length toxin, which lacks ADP-ribosyl transferase, activity, to that of the enzymatic domain alone reveals a salt bridge, between Arg467 of the catalytic domain and Glu348 of domain II that, restrains the substrate binding cleft in a conformation that precludes, NAD+ binding. The refined structures of exotoxin A provide precise models, for the design and interpretation of further studies of the mechanism of, intoxication.
+
<StructureSection load='1ikp' size='340' side='right'caption='[[1ikp]], [[Resolution|resolution]] 1.45&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[1ikp]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IKP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1IKP 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]] 1.45&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></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=1ikp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ikp OCA], [https://pdbe.org/1ikp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ikp RCSB], [https://www.ebi.ac.uk/pdbsum/1ikp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ikp ProSAT]</span></td></tr>
 +
</table>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/TOXA_PSEAE TOXA_PSEAE] An NAD-dependent ADP-ribosyltransferase (ADPRT). Catalyzes the transfer of the ADP ribosyl moiety of oxidized NAD (NAD(+)) onto eukaryotic elongation factor 2 (eEF-2) thus arresting protein synthesis. Has an LD(50) of 65 ng/ml against the human lung epithelial cell line C38.<ref>PMID:18276581</ref>
-
==About this Structure==
+
==See Also==
-
1IKP is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa] with CL and NA as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1IKP OCA].
+
*[[Exotoxin 3D structures|Exotoxin 3D structures]]
-
 
+
== References ==
-
==Reference==
+
<references/>
-
Refined crystallographic structure of Pseudomonas aeruginosa exotoxin A and its implications for the molecular mechanism of toxicity., Wedekind JE, Trame CB, Dorywalska M, Koehl P, Raschke TM, McKee M, FitzGerald D, Collier RJ, McKay DB, J Mol Biol. 2001 Dec 7;314(4):823-37. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11734000 11734000]
+
__TOC__
 +
</StructureSection>
 +
[[Category: Large Structures]]
[[Category: Pseudomonas aeruginosa]]
[[Category: Pseudomonas aeruginosa]]
-
[[Category: Single protein]]
+
[[Category: McKay DB]]
-
[[Category: McKay, D.B.]]
+
[[Category: Trame CB]]
-
[[Category: Trame, C.B.]]
+
[[Category: Wedekind JE]]
-
[[Category: Wedekind, J.E.]]
+
-
[[Category: CL]]
+
-
[[Category: NA]]
+
-
[[Category: all 3 exotoxin a domains]]
+
-
 
+
-
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 17:28:34 2007''
+

Current revision

Pseudomonas Aeruginosa Exotoxin A, P201Q, W281A mutant

PDB ID 1ikp

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1ikp"
Personal tools