Membrane reconstitution of human dihydroorotate dehydrogenase using lipid-detergent micelles

Human dihydroorotate dehydrogenase (DHODH) is an integral membrane protein found in mitochondria involved in the biosynthesis of pyrimidines. DHODH oxidizes dihydroorotate with the simultaneous reduction of ubiquinone Q10 and is a well-validated target for anti-inflammatory and anti-proliferative drugs. We are investigating the mechanisms by which DHODH interacts with Q10 and clinical inhibitors in the inner mitochondrial membrane (IMM) and therefore develop methods to reconstitute it into physiologically lipid bilayers mimicking the IMM using phospholipid-detergent micelles. In this experiment, we propose will investigate for the first time the reconstitution of DHODH into supported bilayers from phospholipid-dodecyl-D-maltoside (DDM) micelles using contrasts variation to determine the composition and structure of the membrane during the deposition process.