Structure of recombinant formate dehydrogenase from Methylobacterium extorquens (MeFDH1)

Abstract

Formate dehydrogenase (FDH) is critical for the conversion between formate and carbon dioxide. Despite its importance, the structural complexity of FDH and difficulties in the production of the enzyme have made it difficult to elucidate its unique physicochemical properties. Here, we purified recombinant Methylobacterium extorquens AM1 FDH (MeFDH1) and used cryo-electron microscopy to determine its structure. We resolved a heterodimeric MeFDH1 structure at a resolution of 2.8 [A], showing a noncanonical active site and a well-embedded Fe-S redox chain relay. In particular, the tungsten bis-molybdopterin guanine dinucleotide active site showed an open configuration with the flexible C-terminal cap domain, suggesting structural and dynamic heterogeneity in the enzyme. SIGNIFICANCE- A recombinant MeFDH1 from an inducible expression system - Structural characterization of recombinant MeFDH1 for its catalytic activity - A dynamic, open configuration of the C-terminal cap domain