Conformational dynamics of the molecular chaperone Hsp90 in complexes with a co-chaperone and anticancer drugs.
The molecular chaperone Hsp90 is essential for the correct folding, maturation and activation of a diverse array of client proteins, including several key constituents of oncogenic processes. Hsp90 has become a focus of cancer research, since it represents a target for direct prophylaxis against mul...
| Main Authors: | , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2007
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| _version_ | 1826295210588504064 |
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| author | Phillips, J Yao, Z Zhang, W McLaughlin, S Laue, E Robinson, C Jackson, SE |
| author_facet | Phillips, J Yao, Z Zhang, W McLaughlin, S Laue, E Robinson, C Jackson, SE |
| author_sort | Phillips, J |
| collection | OXFORD |
| description | The molecular chaperone Hsp90 is essential for the correct folding, maturation and activation of a diverse array of client proteins, including several key constituents of oncogenic processes. Hsp90 has become a focus of cancer research, since it represents a target for direct prophylaxis against multistep malignancy. Hydrogen-exchange mass spectrometry was used to study the structural and conformational changes undergone by full-length human Hsp90beta in solution upon binding of the kinase-specific co-chaperone Cdc37 and two Hsp90 ATPase inhibitors: Radicicol and the first-generation anticancer drug DMAG. Changes in hydrogen exchange pattern in the complexes in regions of Hsp90 remote to the ligand-binding site were observed indicating long-range effects. In particular, the interface between the N-terminal domain and middle domains exhibited significant differences between the apo and complexed forms. For the inhibitors, differences in the interface between the middle domain and the C-terminal domain were also observed. These data provide important insight into the structure of the biologically active form of the protein. |
| first_indexed | 2024-03-07T03:57:32Z |
| format | Journal article |
| id | oxford-uuid:c3619ba0-4bb6-4549-9348-b0fffa75412a |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:57:32Z |
| publishDate | 2007 |
| record_format | dspace |
| spelling | oxford-uuid:c3619ba0-4bb6-4549-9348-b0fffa75412a2022-03-27T06:16:00ZConformational dynamics of the molecular chaperone Hsp90 in complexes with a co-chaperone and anticancer drugs.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c3619ba0-4bb6-4549-9348-b0fffa75412aEnglishSymplectic Elements at Oxford2007Phillips, JYao, ZZhang, WMcLaughlin, SLaue, ERobinson, CJackson, SEThe molecular chaperone Hsp90 is essential for the correct folding, maturation and activation of a diverse array of client proteins, including several key constituents of oncogenic processes. Hsp90 has become a focus of cancer research, since it represents a target for direct prophylaxis against multistep malignancy. Hydrogen-exchange mass spectrometry was used to study the structural and conformational changes undergone by full-length human Hsp90beta in solution upon binding of the kinase-specific co-chaperone Cdc37 and two Hsp90 ATPase inhibitors: Radicicol and the first-generation anticancer drug DMAG. Changes in hydrogen exchange pattern in the complexes in regions of Hsp90 remote to the ligand-binding site were observed indicating long-range effects. In particular, the interface between the N-terminal domain and middle domains exhibited significant differences between the apo and complexed forms. For the inhibitors, differences in the interface between the middle domain and the C-terminal domain were also observed. These data provide important insight into the structure of the biologically active form of the protein. |
| spellingShingle | Phillips, J Yao, Z Zhang, W McLaughlin, S Laue, E Robinson, C Jackson, SE Conformational dynamics of the molecular chaperone Hsp90 in complexes with a co-chaperone and anticancer drugs. |
| title | Conformational dynamics of the molecular chaperone Hsp90 in complexes with a co-chaperone and anticancer drugs. |
| title_full | Conformational dynamics of the molecular chaperone Hsp90 in complexes with a co-chaperone and anticancer drugs. |
| title_fullStr | Conformational dynamics of the molecular chaperone Hsp90 in complexes with a co-chaperone and anticancer drugs. |
| title_full_unstemmed | Conformational dynamics of the molecular chaperone Hsp90 in complexes with a co-chaperone and anticancer drugs. |
| title_short | Conformational dynamics of the molecular chaperone Hsp90 in complexes with a co-chaperone and anticancer drugs. |
| title_sort | conformational dynamics of the molecular chaperone hsp90 in complexes with a co chaperone and anticancer drugs |
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