Abstract |
Certain uropathogenic and neonatal meningitis-causing strains of Escherichia coli express a 114 kDa protein toxin called cytotoxic necrotizing factor 1 (CNF1). The toxin causes alteration of the host cell actin cytoskeleton and promotes bacterial invasion of blood-brain barrier endothelial cells. CNF1 belongs to a unique group of large cytotoxins that cause constitutive activation of Rho guanosine triphosphatases ( GTPases), which are key regulators of the actin cytoskeleton. This group also includes E. coli cytotoxic necrotizing factor 2 (CNF2, 114 kDa) and dermonecrotic toxins ( DNT, 159 kDa) of Bordetella spp. with related sequences occurring in Yersinia spp. Here we show that the catalytic region of CNF1 exhibits a novel protein fold as determined by its 1.83 A resolution crystal structure. The structure reveals that CNF1 has a Cys-His-main chain oxygen catalytic triad reminiscent of enzymes belonging to the catalytic triad superfamily. The position of the catalytic Cys residue at the base of a deep pocket restricts access to potential substrates and helps explain the high specificity of this and related toxins.
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Authors | L Buetow, G Flatau, K Chiu, P Boquet, P Ghosh |
Journal | Nature structural biology
(Nat Struct Biol)
Vol. 8
Issue 7
Pg. 584-8
(Jul 2001)
ISSN: 1072-8368 [Print] United States |
PMID | 11427886
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Bacterial Toxins
- Cytotoxins
- Escherichia coli Proteins
- cytotoxic necrotizing factor type 1
- Histidine
- rho GTP-Binding Proteins
- Cysteine
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Topics |
- Amino Acid Sequence
- Amino Acid Substitution
(genetics)
- Bacterial Toxins
(chemistry, genetics, metabolism)
- Binding Sites
- Catalytic Domain
- Conserved Sequence
(genetics)
- Crystallography, X-Ray
- Cysteine
(genetics, metabolism)
- Cytotoxins
(chemistry, genetics, metabolism)
- Enzyme Activation
- Escherichia coli
(chemistry, genetics)
- Escherichia coli Proteins
- Histidine
(metabolism)
- Models, Molecular
- Molecular Sequence Data
- Mutagenesis
(genetics)
- Protein Structure, Secondary
- Protein Structure, Tertiary
- Sequence Alignment
- Substrate Specificity
- rho GTP-Binding Proteins
(metabolism)
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