New insights into the mechanism of electron transfer within flavohemoglobins: tunnelling pathways, packing density, thermodynamic and kinetic analyses
Literature Information
Emna El Hammi, Chantal Houée-Lévin, Jan Řezáč, Bernard Lévy, Isabelle Demachy, Laura Baciou, Aurélien de la Lande
Flavohemoglobins (FlavoHb) are metalloenzymes catalyzing the reaction of nitric oxide dioxygenation. The iron cation of the heme group needs to be preliminarily reduced to the ferrous state to be catalytically competent. This reduction is triggered by a flavin adenine dinucleotide (FAD) prosthetic group which is localized in a distinct domain of the protein. In this paper we obtain new insights into the internal long range electron transfer (over ca. 12 Å) using a combination of experimental and computational approaches. Employing a time-resolved pulse radiolysis technique we report the first direct measurement of the FADH˙ → HemeFeIII electron transfer rate. A rate constant of (6.8 ± 0.5) × 103 s−1 is found. A large panel of computational approaches are used to provide the first estimation of the thermodynamic characteristics of the internal electron transfer step within flavoHb: both the driving force and the reorganization energy are estimated as a function of the protonated state of the flavin semi-quinone. We also report an analysis of the electron pathways involved in the tunnelling of the electron through the aqueous interface between the globin and the flavin domains.
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