37 research outputs found
How Thioredoxin Dissociates Its Mixed Disulfide
The dissociation mechanism of the thioredoxin (Trx) mixed disulfide complexes is unknown and has been debated for more than twenty years. Specifically, opposing arguments for the activation of the nucleophilic cysteine as a thiolate during the dissociation of the complex have been put forward. As a key model, the complex between Trx and its endogenous substrate, arsenate reductase (ArsC), was used. In this structure, a Cys29Trx-Cys89ArsC intermediate disulfide is formed by the nucleophilic attack of Cys29Trx on the exposed Cys82ArsC-Cys89ArsC in oxidized ArsC. With theoretical reactivity analysis, molecular dynamics simulations, and biochemical complex formation experiments with Cys-mutants, Trx mixed disulfide dissociation was studied. We observed that the conformational changes around the intermediate disulfide bring Cys32Trx in contact with Cys29Trx. Cys32Trx is activated for its nucleophilic attack by hydrogen bonds, and Cys32Trx is found to be more reactive than Cys82ArsC. Additionally, Cys32Trx directs its nucleophilic attack on the more susceptible Cys29Trx and not on Cys89ArsC. This multidisciplinary approach provides fresh insights into a universal thiol/disulfide exchange reaction mechanism that results in reduced substrate and oxidized Trx
Vortex Whistle and Smart Phone Application for Peak Flow Recordings in Asthmatic Children: A Feasibility Study
Influence of Alkylating Reagent Softness on the Regioselectivity in Enolate Ion Alkylation:Â A Theoretical Local Hard and Soft Acids and Bases Study
Application of In-Line Fiber-Optic Raman Spectroscopy to Monitoring Emulsion Polymerization Reactions
Tributyl- and triphenyltin benzoates, phenylacetates, and cinnamates as anion carriers: an electrochemical assessment coupled to structural NMR studies and AM1 calculations
FLWINinfo:eu-repo/semantics/publishe