Metal-Containing Formate Dehydrogenases, a Personal View

Area of Science:

• Biochemistry
• Enzymology
• Bioinorganic Chemistry

Background:

• Metal-containing formate dehydrogenases (FDH) are enzymes that catalyze the reversible oxidation of formate to carbon dioxide.
• These enzymes belong to the dimethylsulfoxide reductase family and feature mononuclear molybdenum cofactor (Moco) or tungsten cofactor (Wco) active sites.
• The active site contains a Mo or W atom coordinated by dithiolene groups, a SeCys or Cys residue, and a sulfido ligand.

Purpose of the Study:

• To discuss the catalytic mechanism of metal-containing formate dehydrogenases.
• To explore the structural and functional similarities between molybdenum- and tungsten-containing FDHs.
• To highlight the differences in catalytic efficiency between SeCys- and Cys-containing FDHs.

Main Methods:

• Review and discussion of existing literature on formate dehydrogenase structure and mechanism.
• Comparative analysis of molybdenum and tungsten active sites and their coordination.
• Examination of the role of different amino acid residues (SeCys vs. Cys) in enzyme activity.

Main Results:

• SeCys-containing FDHs generally exhibit higher turnover numbers compared to Cys-containing enzymes.
• The chemical properties of tungsten (W) and molybdenum (Mo) are analogous, suggesting similar active site structures.
• Evidence supports the conclusion that Mo- and W-containing FDHs share the same fundamental reaction mechanism.

Conclusions:

• Metal-containing FDHs utilize a conserved active site structure involving Mo or W, dithiolenes, a SeCys/Cys residue, and a sulfido ligand.
• Despite similarities, the precise details of the catalytic mechanism for these enzymes are not fully elucidated.
• The study emphasizes the ongoing research into understanding the intricate catalytic processes of formate dehydrogenases.