INQUIMAE   12526
INSTITUTO DE QUIMICA, FISICA DE LOS MATERIALES, MEDIOAMBIENTE Y ENERGIA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Controlling Electron Transfer and Alternative Functions in Metalloproteins
Autor/es:
MURGIDA D. H.
Lugar:
La Plata
Reunión:
Workshop; Workshop on Molecular Systems Engineering Sciences; 2015
Institución organizadora:
INIFTA
Resumen:
Protein electron transfer (ET) reactions constitute the basis of energy transduction in living organisms and involve a variety of fine-tuning mechanisms that have just begun to be uncovered. In this respect, the notion of a ?native? state associated with protein function is not sufficient for successfully describing intra- and inter-protein ET reactions. In this lecture I will present recent combined electrochemical, spectroelectrochemical, spectroscopic and computational studies on the ET reactions of cytochrome c and of the primary electron acceptor of cytochrome c oxidase, the CuA site, in biomimetic complexes. The results show that protein dynamics and thermal fluctuations allow these systems to explore different structural and electronic configurations that are crucial for their function, optimizing the kinetic parameters in different ways. Moreover, electrostatic interactions and local electric fields reshape the free energy surfaces that the proteins explore, in a manner that may be central for regulation of the respiratory electron transport chain. For example, the results reveal the existence of two native-like conformations of cytochrome c that present significantly different reorganization energy (λ). Conversion from the high to the low λ forms is triggered by electrostatic interactions, and involves the rupture of a weak H-bond between first- (M80) and second-sphere (Y67) ligands of the heme iron, as a distinctive feature of the conformational switch. The two flexible Ω loops operate as transducers of the electrostatic signal. On the other hand, the CuA site may populate two alternative ground states that differ in  values and are optimized for electron entry and exit, respectively, through two different and nearly perpendicular pathways. The relative populations of these two redox active states can be modulated through first and second sphere mutations, through minor geometrical distortions and by application of biologically significant electric fields. The physiological relevance of these finding will be critically discussed in terms of a possible regulatory mechanism of the Cyt/CcO ET reaction in vivo.
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