Pub. Date : 2016 Jul
PMID : 27398312
12 Functional Relationships(s)Download |
Sentence | Compound Name | Protein Name | Organism |
| 1 | Mutations Y493G and K546D in human HSP90 disrupt binding of celastrol and reduce interaction with Cdc37. | celastrol | heat shock protein 90 alpha family class A member 1 | Homo sapiens |
| 2 | 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. | celastrol | heat shock protein 90 alpha family class A member 1 | Homo sapiens |
| 3 | However, the HSP90 structure involved in celastrol interaction is not known. | celastrol | heat shock protein 90 alpha family class A member 1 | Homo sapiens |
| 4 | Here, we report a novel celastrol-binding pocket in the HSP90 dimer, predicted by molecular docking. | celastrol | heat shock protein 90 alpha family class A member 1 | Homo sapiens |
| 5 | 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). | celastrol | heat shock protein 90 alpha family class A member 1 | Homo sapiens |
| 6 | 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. | celastrol | heat shock protein 90 alpha family class A member 1 | Homo sapiens |
| 7 | 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. | celastrol | heat shock protein 90 alpha family class A member 1 | Homo sapiens |
| 8 | 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. | celastrol | heat shock protein 90 alpha family class A member 1 | Homo sapiens |
| 9 | 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. | celastrol | heat shock protein 90 alpha family class A member 1 | Homo sapiens |
| 10 | 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. | celastrol | heat shock protein 90 alpha family class A member 1 | Homo sapiens |
| 11 | 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. | celastrol | heat shock protein 90 alpha family class A member 1 | Homo sapiens |
| 12 | 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. | celastrol | heat shock protein 90 alpha family class A member 1 | Homo sapiens |