| Texto completo | |
| Autor(es): |
Libardi, Silvia H.
;
Ahmad, Anees
;
Ferreira, Francis B.
;
Oliveira, Ronaldo J.
;
Caruso, Icaro P.
;
Melo, Fernando A.
;
de Albuquerque, Sergio
;
Cardoso, Daniel R.
;
Burtoloso, Antonio C. B.
;
Borges, Julio C.
Número total de Autores: 10
|
| Tipo de documento: | Artigo Científico |
| Fonte: | International Journal of Biological Macromolecules; v. 259, p. 11-pg., 2024-01-15. |
| Resumo | |
Old Yellow Enzymes (OYEs) are flavin-dependent redox enzymes that promote the asymmetric reduction of activated alkenes. Due to the high importance of flavoenzymes in the metabolism of organisms, the interaction between OYEs from the parasites Trypanosoma cruzi and Leishmania braziliensis and three diterpene icetexanes (brussonol and two analogs), were evaluated in the present study, and differences in the binding mechanism and inhibition capacity of these molecules were examined. Although the aforementioned compounds showed poor and negligible activities against T. cruzi and L. braziliensis cells, respectively, the experiments with the purified enzymes indicated that the interaction occurs by divergent mechanisms. Overall, the ligands' inhibitory effect depends on their accessibility to the N5 position of the flavin's isoalloxazine ring. The results also indicated that the OYEs found in both parasites share structural similarities and showed affinities for the diterpene icetexanes in the same range. Nevertheless, the interaction between OYEs and ligands is directed by enthalpy and/or entropy in distinct ways. In conclusion, the binding site of both OYEs exhibits remarkable plasticity, and a large range of different molecules, including that can be substrates and inhibitors, can bind this site. This plasticity should be considered in drug design using OYE as a target. (AU) | |
| Processo FAPESP: | 14/07206-6 - Estudos da HSP70 mitocondrial de humanos e de protozoários: abordagem estrutural e funcional |
| Beneficiário: | Julio Cesar Borges |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 18/05576-1 - Estudo cinético e mecanístico da atividade enzimática das old yellow enzymes de Leishmania braziliensis e Trypanosoma cruzi |
| Beneficiário: | Silvia Helena Libardi |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 11/23110-0 - Uso da calorimetria de titulação isotérmica para a determinação de propriedades termodinâmicas de interação de proteína-ligante e proteína-proteína |
| Beneficiário: | Julio Cesar Borges |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 12/50161-8 - Estudo da estrutura e função da chaperona Hsp90 com ênfase no seu papel em homeostase celular |
| Beneficiário: | Carlos Henrique Inacio Ramos |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |
| Processo FAPESP: | 17/07335-9 - Estudos das isoformas da HSP70 humana residentes no citoplasma e mitocôndria e de seus oligômeros de alta massa molecular: interação com co-chaperonas e proteínas clientes |
| Beneficiário: | Julio Cesar Borges |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |