title: New insights into the mechanism of electron transfer within flavohemoglobins: tunnelling pathways, packing density, thermodynamic and kinetic analyses.
abstract: 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˙→ HemeFe(III) electron transfer rate. A rate constant of (6.8 ± 0.5) × 10(3) 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.
authors.affiliation: Laboratoire de Chimie Physique-CNRS UMR 8000, Université Paris-Sud. Bât. 349-350, Campus d'Orsay. 15, avenue Jean Perrin, 91405 Orsay Cedex, France.
authors.forename: Emna
authors.initials: E
authors.lastname: El Hammi
authors.forename: Chantal
authors.initials: C
authors.lastname: Houée-Lévin
authors.forename: Jan
authors.initials: J
authors.lastname: Řezáč
authors.forename: Bernard
authors.initials: B
authors.lastname: Lévy
authors.forename: Isabelle
authors.initials: I
authors.lastname: Demachy
authors.forename: Laura
authors.initials: L
authors.lastname: Baciou
authors.forename: Aurélien
authors.initials: A
authors.lastname: de la Lande
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D020118:Cupriavidus necator / Q000737:chemistry / Q000378:metabolism*; D004579:Electron Transport; D005182:Flavin-Adenine Dinucleotide / Q000737:chemistry / Q000378:metabolism*; D006420:Hemeproteins / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D008958:Models, Molecular; D013816:Thermodynamics
chemical_list: D001426:Bacterial Proteins; D006420:Hemeproteins; C086193:flavohemoprotein, Bacteria; D005182:Flavin-Adenine Dinucleotide