Crystallographic analyses of the FdsBG subcomplex of the cytosolic formate dehydrogenase FdsDABG from Cupriavidus necator

Abstract

The soluble molybdenum-containing, NAD+-dependent formate dehydrogenase FdsDABG from Cupriavidus necator belongs to the NADH dehydrogenase superfamily and catalyzes the oxidation of formate to CO2 and the reduction of NAD+ to NADH. Here, we present the first description of the crystal structure of the FdsBG subcomplex with and without bound NADH. Compared to other NADH dehydrogenases, FMN is closer to both iron-sulfur clusters, Fe4S4 in FdsB and Fe2S2 in FdsG. Based on the NADH-bound structure, we conclude that the nicotinamide ring of NADH can only access the re-face of FMN. However, the binding of NADH reduces the affinity of the isoalloxazine ring of FMN and allows for a conformational change of the residues that are known to undergo an oxidation state-dependent peptide flip in canonical NADH dehydrogenases.