ArticleFEBS open bio2016
Mutations Y493G and K546D in human HSP90 disrupt binding of celastrol and reduce interaction with Cdc37.
Article in FEBS open bio, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
3 citing papers in PubMed, 11 citations in OpenAlex.
- Heat shock protein 90 inhibition and multi-target approach to maximize cardioprotection in ischaemic injury.British journal of pharmacology · 2020Review
- Therapeutic Potential of the Hsp90/Cdc37 Interaction in Neurodegenerative Diseases.Frontiers in neuroscience · 2019Review
- Celastrol attenuates ventilator induced lung injury in mouse through inhibition of MAPK pathway.International journal of clinical and experimental pathology · 2017Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Celastrol, a natural compound derived from the Chinese herb Tripterygium wilfordii Hook F, has been proven to inhibit heat shock protein 90 (HSP90) activity and has attracted much attention because of its promising effects in cancer treatment and in ameliorating degenerative neuron diseases. However, the HSP90 structure involved in celastrol interaction is not known. Here, we report a novel celastrol-binding pocket in the HSP90 dimer, predicted by molecular docking. Mutation of the two key binding pocket amino acids (Lys546 and Tyr493) disrupted the binding of celastrol to HSP90 dimers, as detected by isothermal titration calorimetry (ITC). Interestingly, such mutations also reduced binding between HSP90 and the cochaperone Cdc37, thus providing a new explanation for reported findings that celastrol shows more obvious effects in disrupting binding between HSP90 and Cdc37 than between HSP90 and other cochaperones. In short, our work discloses a novel binding pocket in HSP90 dimer for celastrol and provides an explanation as to why celastrol has a strong effect on HSP90 and Cdc37 binding.
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Registered trials
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