RESUMO
Peroxiredoxins catalyze the reduction of peroxides, a process of vital importance to survive oxidative stress. A nucleophilic cysteine, also known as the peroxidatic cysteine, is responsible for this catalytic process. We used the Mycobacterium tuberculosis alkyl hydroperoxide reductase E (MtAhpE) as a model to investigate the effect of the chemical environment on the specificity of the reaction. Using an integrative structural (R116A - PDB ; F37H - PDB ), kinetic and computational approach, we explain the mutational effects of key residues in its environment. This study shows that the active site residues are specifically oriented to create an environment which selectively favours a reaction with peroxides.
Assuntos
Mycobacterium tuberculosis/enzimologia , Peroxirredoxinas/metabolismo , Domínio Catalítico , Cinética , Simulação de Dinâmica Molecular , Oxirredução , Peróxidos/química , Peróxidos/metabolismo , Peroxirredoxinas/química , Peroxirredoxinas/genética , Conformação ProteicaRESUMO
This paper concerns the accurate description of the surface oxygen reactivity for the alkaline earth metal oxides using local DFT-based reactivity indices. The cumbersome periodic boundary conditions calculations, typically required to probe the reactivity of such systems, are avoided by the construction of a reliable cluster model. The standard Fukui function concept of conceptual DFT is generalized to include the contribution from not only the HOMO and the LUMO but also from other chemically relevant orbitals. Results prove that this approach is a valuable and straightforward alternative to the reactivity calculation of extended systems.