Abstract
Recent reports have indicated that insect antimicrobial peptides kill bacteria by inhibiting the molecular chaperone DnaK. It was proposed that the antimicrobial peptide, all-L-pyrrhocoricin (L-PYR), binds to two sites on DnaK, the conventional substrate-binding site and the multi-helical C-terminal lid, and that inhibition of DnaK comes about from the lid mode of binding. In this report, we show using two different assays that L-PYR binds to and stimulates the ATPase activity of both wild-type and a lidless variant of DnaK. Our study shows that L-PYR interacts with DnaK much like the all-L NR (NRLLLTG) peptide, which is known to bind in the conventional substrate-binding site of DnaK. L-PYR antimicrobial activity is thus a consequence of the competitive inhibition of bacterial DnaK.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenosine Triphosphatases / chemistry*
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Animals
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Anti-Bacterial Agents / chemistry*
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Anti-Bacterial Agents / pharmacology
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Anti-Infective Agents / chemistry*
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Anti-Infective Agents / pharmacology
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Antimicrobial Cationic Peptides / chemistry*
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Antimicrobial Cationic Peptides / pharmacology
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Binding Sites
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Dose-Response Relationship, Drug
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HSP70 Heat-Shock Proteins / metabolism
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Insect Proteins*
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Insecta
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Kinetics
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Models, Chemical
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Models, Molecular
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Peptides / chemistry
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Protein Binding
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Protein Structure, Tertiary
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Spectrometry, Fluorescence
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Temperature
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Time Factors
Substances
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Anti-Bacterial Agents
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Anti-Infective Agents
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Antimicrobial Cationic Peptides
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HSP70 Heat-Shock Proteins
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Insect Proteins
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Peptides
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pyrrhocoricin protein, Pyrrhocoris apterus
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Adenosine Triphosphatases