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| - | [[Image:1ikp.jpg|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_1ikp| PDB=1ikp | SCENE= }} | | {{STRUCTURE_1ikp| PDB=1ikp | SCENE= }} |
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| - | '''Pseudomonas Aeruginosa Exotoxin A, P201Q, W281A mutant'''
| + | ===Pseudomonas Aeruginosa Exotoxin A, P201Q, W281A mutant=== |
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| - | ==Overview==
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| - | 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.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_11734000}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 11734000 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_11734000}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Wedekind, J E.]] | | [[Category: Wedekind, J E.]] |
| | [[Category: All 3 exotoxin a domain]] | | [[Category: All 3 exotoxin a domain]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 20:06:26 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 13:24:41 2008'' |
Revision as of 10:24, 1 July 2008
Template:STRUCTURE 1ikp
Pseudomonas Aeruginosa Exotoxin A, P201Q, W281A mutant
Template:ABSTRACT PUBMED 11734000
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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