Electron transfer is at the heart of many biochemical processes (respiratory chain, enzyme catalysis…). Our team uses molecular simulation to understand how proteins control the speed and directionality of electron transfer. Over the past few years, we have pushed Marcus’ theory to the limit in the case of ultra-rapid photo-induced electron transfers in cryptochromes and photolysases (see below). More recently, we’ve turned our attention to electron transfer in membrane proteins.
Electron transfers in NADPH oxydases
Cells excel at transporting electrons on a microscopic scale to meet their metabolic needs. One example is class 2 NADPH oxidases (NOX2), which play a vital role in immune defense. NOXs are machines that produce toxic chemical species such as superoxide anion (O2°-) to destroy pathogens previously trapped in phagosomes, a kind of small lipid sacs formed around them. At the molecular level, the details of the mechanism by which superoxide anions are produced remain unknown, although the first three-dimensional structures of NOX catalytic cores to appear since 2017 are providing some insight. The electrons required to reduce oxygen are said to transit from the outside to the inside of the phagosome via transmembrane electron transfer.
This research project is currently developped in collaboration with Dr Marc Baaden (CNRS, Laboratoire de Biochimie Theorique), Dr Laura Baciou (CNRS, ICP) in the context of the ANR SuperET project.
Publications: Mechanistic insights on heme-to-heme transmembrane electron transfer within NADPH oxydases from atomistic simulations
Electron transfers in cytochromes bd
The respiratory terminal oxidases found in a typical respiratory chain are heme-copper oxidases. In some prokaryotes though, bd-type oxidases are also found in addition to heme-copper oxidases. The two well-known membrane-integrated terminal oxidases, heme-copper oxidase and bd-type oxidase (cytochrome bd) catalyse the reduction of molecular oxygen to water using different substrates, typically a quinol molecule. Owing to the absence of cyt bd in Eukaryotes and to the fact that bd-type terminal oxidases are crucial for prokaryotes in reduced oxygen environments, these proteins are of high interest as pharmaceutical targets.