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.