1ikp
From Proteopedia
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| - | [[Image:1ikp.jpg|left|200px]] | + | [[Image:1ikp.jpg|left|200px]] |
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| - | '''Pseudomonas Aeruginosa Exotoxin A, P201Q, W281A mutant''' | + | {{Structure |
| + | |PDB= 1ikp |SIZE=350|CAPTION= <scene name='initialview01'>1ikp</scene>, resolution 1.45Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene> and <scene name='pdbligand=NA:SODIUM ION'>NA</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= PE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=287 Pseudomonas aeruginosa]) | ||
| + | }} | ||
| + | |||
| + | '''Pseudomonas Aeruginosa Exotoxin A, P201Q, W281A mutant''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1IKP is a [ | + | 1IKP is a [[Single protein]] structure of sequence from [http://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]. |
==Reference== | ==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:[http:// | + | 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://www.ncbi.nlm.nih.gov/pubmed/11734000 11734000] |
[[Category: Pseudomonas aeruginosa]] | [[Category: Pseudomonas aeruginosa]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: CL]] | [[Category: CL]] | ||
[[Category: NA]] | [[Category: NA]] | ||
| - | [[Category: all 3 exotoxin a | + | [[Category: all 3 exotoxin a domain]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:51:41 2008'' |
Revision as of 09:51, 20 March 2008
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| , resolution 1.45Å | |||||||
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| Ligands: | and | ||||||
| Gene: | PE (Pseudomonas aeruginosa) | ||||||
| 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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