1ikp
From Proteopedia
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|PDB= 1ikp |SIZE=350|CAPTION= <scene name='initialview01'>1ikp</scene>, resolution 1.45Å | |PDB= 1ikp |SIZE=350|CAPTION= <scene name='initialview01'>1ikp</scene>, resolution 1.45Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene> | + | |LIGAND= <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= PE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=287 Pseudomonas aeruginosa]) | |GENE= PE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=287 Pseudomonas aeruginosa]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1aer|1AER]], [[1dma|1DMA]], [[1ikq|1ikq]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ikp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ikp OCA], [http://www.ebi.ac.uk/pdbsum/1ikp PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1ikp RCSB]</span> | ||
}} | }} | ||
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[[Category: Trame, C B.]] | [[Category: Trame, C B.]] | ||
[[Category: Wedekind, J E.]] | [[Category: Wedekind, J E.]] | ||
| - | [[Category: CL]] | ||
| - | [[Category: NA]] | ||
[[Category: all 3 exotoxin a domain]] | [[Category: all 3 exotoxin a domain]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:21:07 2008'' |
Revision as of 18:21, 30 March 2008
| |||||||
| , resolution 1.45Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Gene: | PE (Pseudomonas aeruginosa) | ||||||
| Related: | 1AER, 1DMA, 1ikq
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Pseudomonas Aeruginosa Exotoxin A, P201Q, W281A mutant
Overview
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.
About this Structure
1IKP is a Single protein structure of sequence from Pseudomonas aeruginosa. Full crystallographic information is available from OCA.
Reference
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:11734000
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