Abstract
The structure of BPSL1549, a protein of unknown function from Burkholderia pseudomallei, reveals a similarity to Escherichia coli cytotoxic necrotizing factor 1. We found that BPSL1549 acted as a potent cytotoxin against eukaryotic cells and was lethal when administered to mice. Expression levels of bpsl1549 correlate with conditions expected to promote or suppress pathogenicity. BPSL1549 promotes deamidation of glutamine-339 of the translation initiation factor eIF4A, abolishing its helicase activity and inhibiting translation. We propose to name BPSL1549 Burkholderia lethal factor 1.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Motifs
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Animals
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Bacterial Proteins / chemistry*
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Bacterial Proteins / genetics
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Bacterial Proteins / metabolism
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Bacterial Proteins / toxicity*
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Bacterial Toxins / chemistry*
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Bacterial Toxins / genetics
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Bacterial Toxins / metabolism
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Bacterial Toxins / toxicity*
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Burkholderia pseudomallei / chemistry*
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Burkholderia pseudomallei / pathogenicity*
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Catalytic Domain
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Cell Line
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Crystallography, X-Ray
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Cytotoxins / chemistry
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Cytotoxins / genetics
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Cytotoxins / metabolism
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Cytotoxins / toxicity
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Escherichia coli Proteins / chemistry
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Eukaryotic Initiation Factor-4A / antagonists & inhibitors*
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Eukaryotic Initiation Factor-4A / metabolism
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Glutamine / metabolism
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Humans
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Mice
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Mice, Inbred BALB C
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Models, Molecular
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Mutant Proteins / toxicity
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Peptide Chain Initiation, Translational / drug effects
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Protein Binding
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Protein Conformation
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Protein Structure, Secondary
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Protein Structure, Tertiary
Substances
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BPSL1549 protein, Burkholderia pseudomallei
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Bacterial Proteins
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Bacterial Toxins
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Cytotoxins
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Escherichia coli Proteins
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Mutant Proteins
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Glutamine
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cytotoxic necrotizing factor type 1
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Eukaryotic Initiation Factor-4A