Cyclic lipopeptide antibiotics bind to the N-terminal domain of the prokaryotic Hsp90 to inhibit the chaperone activity
| Autor: | Yasumitsu Kondoh, Keigo Sueoka, Hitoshi Nakamoto, Shun Minagawa, Hiroyuki Osada |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Protein Folding
Hot Temperature Surface Properties Light-Harvesting Protein Complexes Ligands Peptides Cyclic Biochemistry law.invention Lipopeptides Bacterial Proteins law medicine Protein Interaction Domains and Motifs HSP90 Heat-Shock Proteins Molecular Biology Polymyxin B Adenosine Triphosphatases Synechococcus Microbial Viability biology Colistin Cell Biology biology.organism_classification Hsp90 Peptide Fragments Recombinant Proteins Anti-Bacterial Agents High-Throughput Screening Assays Hsp70 Chaperone (protein) Mutation biology.protein Recombinant DNA Protein folding Hydrophobic and Hydrophilic Interactions medicine.drug |
| Zdroj: | Biochemical Journal. 435:237-246 |
| ISSN: | 1470-8728 0264-6021 |
| DOI: | 10.1042/bj20100743 |
| Popis: | Chemical arrays were employed to screen ligands for HtpG, the prokaryotic homologue of Hsp (heat-shock protein) 90. We found that colistins and the closely related polymyxin B interact physically with HtpG. They bind to the N-terminal domain of HtpG specifically without affecting its ATPase activity. The interaction caused inhibition of chaperone function of HtpG that suppresses thermal aggregation of substrate proteins. Further studies were performed with one of these cyclic lipopeptide antibiotics, colistin sulfate salt. It inhibited the chaperone function of the N-terminal domain of HtpG. However, it inhibited neither the chaperone function of the middle domain of HtpG nor that of other molecular chaperones such as DnaK, the prokaryotic homologue of Hsp70, and small Hsp. The addition of colistin sulfate salt increased surface hydrophobicity of the N-terminal domain of HtpG and induced oligomerization of HtpG and its N-terminal domain. These structural changes are discussed in relation to the inhibition of the chaperone function. |
| Databáze: | OpenAIRE |
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