| Author | Lima, Carlyle Ribeiro | |
| Author | Santos, Deborah Antunes dos | |
| Author | Raúl Caffarena, Ernesto | |
| Author | Carels, Nicolas | |
| Access date | 2024-10-04T17:09:01Z | |
| Available date | 2024-10-04T17:09:01Z | |
| Document date | 2024 | |
| Citation | LIMA, Carlyle Ribeiro et al. Structural characterization of heat shock protein 90β and molecular interactions with Geldanamycin and Ritonavir: a computational study. International Journal of Molecular Sciences, v. 25, n. 16, p. 1-20, 12 Aug. 2024. | |
| ISSN | 1661-6596 | |
| URI | https://www.arca.fiocruz.br/handle/icict/66314 | |
| Description | Produção científica do Laboratório de Genômica Aplicada e Bioinovações. | pt_BR |
| Sponsorship | This research received external funding from National Research Council (CNPQ) through the National Institute for Science and Technology on Innovation in Diseases of Neglected Populations (INCT-IDPN), Coordination for the Improvement of Higher Education Personnel (CAPES, BEX Process 88887.319299/2019-00). Carlyle Ribeiro Lima received a scholarship (VPPIS-003-FIO-20) from Foundation for Scientific and Technological Development in Health (FIOTEC). | |
| Language | eng | en_US |
| Publisher | MDPI | |
| Rights | open access | |
| Title | Structural characterization of heat shock protein 90β and molecular interactions with Geldanamycin and Ritonavir: a computational study | en_US |
| Type | Article | |
| DOI | 10.3390/ijms25168782 | |
| Abstract | Drug repositioning is an important therapeutic strategy for treating breast cancer. Hsp90β chaperone is an attractive target for inhibiting cell progression. Its structure has a disordered and flexible linker region between the N-terminal and central domains. Geldanamycin was the first Hsp90β inhibitor to interact specifically at the N-terminal site. Owing to the toxicity of geldanamycin, we investigated the repositioning of ritonavir as an Hsp90β inhibitor, taking advantage of its proven efficacy against cancer. In this study, we used molecular modeling techniques to analyze the contribution of the Hsp90β linker region to the flexibility and interaction between the ligands geldanamycin, ritonavir, and Hsp90β. Our findings indicate that the linker region is responsible for the fluctuation and overall protein motion without disturbing the interaction between the inhibitors and the N-terminus. We also found that ritonavir established similar interactions with the substrate ATP triphosphate, filling the same pharmacophore zone. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Laboratório de Modelagem de Sistemas Biológicos. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Aplicada e Bioinovações. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Presidência. Programa de Computação Científica. Grupo de Biofísica Computacional e Modelagem Molecular. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Laboratório de Modelagem de Sistemas Biológicos. Rio de Janeiro, RJ, Brasil. | |
| Subject | Cancer | en_US |
| Subject | Hsp9β | en_US |
| Subject | Ritonavir | en_US |
| Subject | Geldanamycin | en_US |
| Subject | Drug repurposing | en_US |
| Subject | Chemical ligations | en_US |
| Subject | Molecular docking | en_US |
| Subject | Molecular dynamics | en_US |
| e-ISSN | 1422-0067 | |
| xmlui.metadata.dc.subject.ods | 03 Saúde e Bem-Estar | |
| xmlui.metadata.dc.subject.ods | 09 Indústria, inovação e infraestrutura | |
| xmlui.metadata.dc.subject.ods | 17 Parcerias e meios de implementação | |
