NADPH oxidases (NOX) are unique enzymes producing superoxide to destroy pathogens. Flavocytochrome Cyt b558 is the core protein which is inserted in the membrane of phagosomes and catalyses the last step of superoxide production. The latter consists in the transfer of two electrons from a reduced flavin encompassed in the reductase domain across the membrane domain to reduce two dioxygen molecules. The precise molecular mechanism permitting to couple transmembrane electron transfer to superoxide production has however remained elusive so far.
The recent resolution of NOX transmembrane proteins has revealed some structural features regarding the redox cofactors (a flavin and two hemes) that allow the electrons to be transferred through the membrane. It opens the way to a better understanding of the functionning of NOX.
The SuperET project aims at using a combination of experiments and molecular simulations to unravel the mechanisms that lead to the production of superoxide by NOX. It gathers 4 teams from 3 different laboratories tha will join their expertise in radiolysis, spectrokinetics and theroretical chemistry to tackle this issue.