Abstract 2795 Defining the Catalytic Sequences of Dihydroorotate Dehydrogenase 1B from Lactococcus lactis Using Anaerobic Transient State Methods

Dihydroorotate dehydrogenase (DHOD) is a flavoenzyme that catalyzes the fourth step of the de novo pyrimidine nucleotide biosynthesis, the conversion of dihydroorotate to orotate. DHOD inhibitors have shown promise as antiviral agent against, ebola, influenza, Epstein Barr and picornavirus. Other DHOD inhibitors are being developed as treatments for rheumatoid arthritis, malaria, and cancer. In Lactococcus Lactis, there are two members of Class 1 DHODs, class 1A and 1B. The class 1B form is dimer of heterodimers comprised of two proteins (PyrD;PyrK) that together have three cofactors: a flavin mononucleotide (FMN) and a flavin adenine dinucleotide (FAD) and an Fe2S2 cluster that lies roughly equidistant from each flavin.