Details
| Original language | English |
|---|---|
| Pages (from-to) | 2601-2605 |
| Number of pages | 5 |
| Journal | Biochemistry |
| Volume | 57 |
| Issue number | 18 |
| Early online date | 17 Apr 2018 |
| Publication status | Published - 8 May 2018 |
Abstract
The heat shock protein 90 (Hsp90) family plays a critical role in maintaining the homeostasis of the intracellular environment for human and prokaryotic cells. Hsp90 orthologues were identified as important target proteins for cancer and plant disease therapies. It was shown that gambogic acid (GBA) has the potential to inhibit human Hsp90. However, it is unknown whether it is also able to act on the bacterial high-temperature protein (HtpG) analogue. In this work, we screened GBA and nine other novel potential Hsp90 inhibitors using a miniaturized high-throughput protein microarray-based assay and found that GBA shows an inhibitory effect on different Hsp90s after dissimilarity analysis of the protein sequence alignment. The dissociation constant of GBA and HtpG Xanthomonas (XcHtpG) computed from microscale thermophoresis is 682.2 ± 408 μM in the presence of ATP, which is indispensable for the binding of GBA to XcHtpG. Our results demonstrate that GBA is a promising Hsp90/HtpG inhibitor. The work further demonstrates that our assay concept has great potential for finding new potent Hsp/HtpG inhibitors.
Keywords
- Adenosine Triphosphate/chemistry, Amino Acid Sequence/genetics, Bacterial Proteins/antagonists & inhibitors, Fluorescence, HSP90 Heat-Shock Proteins/antagonists & inhibitors, Hot Temperature, Humans, Protein Binding/drug effects, Xanthomonas/chemistry, Xanthones/chemistry
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Biochemistry
Sustainable Development Goals
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In: Biochemistry, Vol. 57, No. 18, 08.05.2018, p. 2601-2605.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - The Noncompetitive Effect of Gambogic Acid Displaces Fluorescence-Labeled ATP but Requires ATP for Binding to Hsp90/HtpG
AU - Yue, Qing
AU - Stahl, Frank
AU - Plettenburg, Oliver
AU - Kirschning, Andreas
AU - Warnecke, Athanasia
AU - Zeilinger, Carsten
N1 - © 2018 American Chemical Society
PY - 2018/5/8
Y1 - 2018/5/8
N2 - The heat shock protein 90 (Hsp90) family plays a critical role in maintaining the homeostasis of the intracellular environment for human and prokaryotic cells. Hsp90 orthologues were identified as important target proteins for cancer and plant disease therapies. It was shown that gambogic acid (GBA) has the potential to inhibit human Hsp90. However, it is unknown whether it is also able to act on the bacterial high-temperature protein (HtpG) analogue. In this work, we screened GBA and nine other novel potential Hsp90 inhibitors using a miniaturized high-throughput protein microarray-based assay and found that GBA shows an inhibitory effect on different Hsp90s after dissimilarity analysis of the protein sequence alignment. The dissociation constant of GBA and HtpG Xanthomonas (XcHtpG) computed from microscale thermophoresis is 682.2 ± 408 μM in the presence of ATP, which is indispensable for the binding of GBA to XcHtpG. Our results demonstrate that GBA is a promising Hsp90/HtpG inhibitor. The work further demonstrates that our assay concept has great potential for finding new potent Hsp/HtpG inhibitors.
AB - The heat shock protein 90 (Hsp90) family plays a critical role in maintaining the homeostasis of the intracellular environment for human and prokaryotic cells. Hsp90 orthologues were identified as important target proteins for cancer and plant disease therapies. It was shown that gambogic acid (GBA) has the potential to inhibit human Hsp90. However, it is unknown whether it is also able to act on the bacterial high-temperature protein (HtpG) analogue. In this work, we screened GBA and nine other novel potential Hsp90 inhibitors using a miniaturized high-throughput protein microarray-based assay and found that GBA shows an inhibitory effect on different Hsp90s after dissimilarity analysis of the protein sequence alignment. The dissociation constant of GBA and HtpG Xanthomonas (XcHtpG) computed from microscale thermophoresis is 682.2 ± 408 μM in the presence of ATP, which is indispensable for the binding of GBA to XcHtpG. Our results demonstrate that GBA is a promising Hsp90/HtpG inhibitor. The work further demonstrates that our assay concept has great potential for finding new potent Hsp/HtpG inhibitors.
KW - Adenosine Triphosphate/chemistry
KW - Amino Acid Sequence/genetics
KW - Bacterial Proteins/antagonists & inhibitors
KW - Fluorescence
KW - HSP90 Heat-Shock Proteins/antagonists & inhibitors
KW - Hot Temperature
KW - Humans
KW - Protein Binding/drug effects
KW - Xanthomonas/chemistry
KW - Xanthones/chemistry
UR - http://www.scopus.com/inward/record.url?scp=85046375367&partnerID=8YFLogxK
U2 - 10.1021/acs.biochem.8b00155
DO - 10.1021/acs.biochem.8b00155
M3 - Article
C2 - 29664615
AN - SCOPUS:85046375367
VL - 57
SP - 2601
EP - 2605
JO - Biochemistry
JF - Biochemistry
SN - 0006-2960
IS - 18
ER -