| Texto completo | |
| Autor(es): |
Arantes, Guilherme M.
Número total de Autores: 1
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| Tipo de documento: | Artigo Científico |
| Fonte: | JOURNAL OF CHEMICAL INFORMATION AND MODELING; v. 65, n. 5, p. 10-pg., 2025-02-26. |
| Resumo | |
Proton translocation catalyzed by cytochrome bc 1 (respiratory complex III) during coenzyme-Q redox cycling is a critical bioenergetic process, yet its detailed molecular mechanism remains incompletely understood. In this study, the energetics of the long-range proton transfers through multiple proton-conducting wires in the Qo site of the bc 1 complex was investigated computationally using hybrid QM/MM simulations and a specialized reaction coordinate. Key reactive groups and proton transfer mechanisms were characterized, confirming the propionate-A group of heme b L as a plausible proton acceptor. Upon coenzyme-Q oxidation, a Grotthuss hopping mechanism is activated, facilitating proton transfer along three distinct pathways with comparable barriers and stability. These pathways operate redundantly, forming a robust proton-conducting network, and account for the unusual experimental behavior observed in single-point mutations. Energetic analyses exclude charged closed-shell species as likely intermediates and propose a reaction sequence for coenzyme-Q oxidation proceeding as QH2 -> QH center dot -> Q0, either via coupled proton-electron transfers or stepwise mechanisms involving open-shell intermediates. These findings elucidate mechanistic details of the Q-cycle and improve our understanding of the catalytic reactions supporting redox-activated proton transfer in respiratory enzymes. (AU) | |
| Processo FAPESP: | 23/00934-5 - Metodologias computacionais para simulação de transferência acoplada próton-elétron em biomoléculas |
| Beneficiário: | Guilherme Menegon Arantes |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |