Formate dehydrogenases are a set of

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...

s that catalyse the oxidation of formate to

carbon dioxide Carbon dioxide ( chemical formula ) is a chemical compound made up of molecules that each have one carbon atom covalently double bonded to two oxygen atoms. It is found in the gas state at room temperature. In the air, carbon dioxide is trans ...

, donating the electrons to a second substrate, such as NAD⁺ in formate:NAD+ oxidoreductase () or to a

cytochrome Cytochromes are redox-active proteins containing a heme, with a central Fe atom at its core, as a cofactor. They are involved in electron transport chain and redox catalysis. They are classified according to the type of heme and its mode of bi ...

in formate:ferricytochrome-b1 oxidoreductase (). This family of enzymes has attracted attention as inspiration or guidance on methods for the carbon dioxide fixation, relevant to

global warming In common usage, climate change describes global warming—the ongoing increase in global average temperature—and its effects on Earth's climate system. Climate change in a broader sense also includes previous long-term changes to E ...

Function

NAD-dependent formate dehydrogenases are important in

methylotroph Methylotrophs are a diverse group of microorganisms that can use reduced one-carbon compounds, such as methanol or methane, as the carbon source for their growth; and multi-carbon compounds that contain no carbon-carbon bonds, such as dimethyl e ...

yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constit ...

and

bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of prokaryotic microorganisms. Typically a few micrometr ...

, being vital in the catabolism of C1 compounds such as methanol. The cytochrome-dependent enzymes are more important in anaerobic metabolism in prokaryotes. For example, in '' E. coli'', the formate:ferricytochrome-b1 oxidoreductase is an intrinsic membrane protein with two subunits and is involved in anaerobic nitrate respiration. NAD-dependent reaction Formate + NAD⁺ CO₂ + NADH + H⁺ Cytochrome-dependent reaction Formate + 2 ferricytochrome b1 CO₂ + 2 ferrocytochrome b1 + 2 H⁺

Molybdopterin, molybdenum and selenium dependence

The metal-dependent Fdh's feature Mo or W at their active sites. These active sites resemble the motif seen in

DMSO reductase DMSO reductase is a molybdenum-containing enzyme that catalyzes reduction of dimethyl sulfoxide (DMSO) to dimethyl sulfide (DMS). This enzyme serves as the terminal reductase under anaerobic conditions in some bacteria, with DMSO being the ter ...

, with two

molybdopterin Molybdopterins are a class of cofactors found in most molybdenum-containing and all tungsten-containing enzymes. Synonyms for molybdopterin are: MPT and pyranopterin-dithiolate. The nomenclature for this biomolecule can be confusing: Molybdopteri ...

cofactors bound to Mo/W in a bidentate fashion. The fifth and sixth ligands are sulfide and either cysteinate or selenocysteinate. The mechanism of action appears to involve 2e redox of the metal centers, induced by hydride transfer from formate and release of

: : : In this scheme, represents the four thiolate-like ligands provided by the two

dithiolene Dithiolene metal complexes are complexes containing 1,2-dithiolene ligands. 1,2-Dithiolene ligands, a particular case of 1,2-dichalcogenolene species, are unsaturated bidentate ligand wherein the two donor atoms are sulfur. 1,2-Dithiolene metal ...

cofactors, the

s. The dithiolene and cysteinyl/selenocysteinyl ligands are redox-innocent. In terms of the molecular details, the mechanism remains uncertain, despite numerous investigations. Most mechanisms assume that formate does not coordinate to Mo/W, in contrast to typical Mo/W oxo-transferases (e.g., dmso reductase). A popular mechanistic proposal entails transfer of H^- from formate to the Mo/W^VI=S group. Formate Dehydrogenase 1kqf overall protein 1 (KC)

Formate Dehydrogenase 1kqf overall protein 1 (KC)

Transmembrane domain

Formate dehydrogenase consists of two transmembrane domains; three α-helices of the β-subunit and four transmembrane helices from the gamma-subunit. The β-subunit of formate dehydrogenase is present in the periplasm with a single transmembrane α-helix spanning the membrane by anchoring the β-subunit to the inner-membrane surface. The β-subunit has two subdomains, where each subdomain has two Fe-4Sferredoxin clusters. The judicious alignment of the Fe-4Sclusters in a chain through the subunit have low separation distances, which allow rapid electron flow through Fe-4S1, Fe-4S4, Fe-4S2, and Fe-4S3 to the periplasmic heme b in the γ-subunit. The electron flow is then directed across the membrane to a cytoplasmic heme b in the γ-subunit . The γ-subunit of formate dehydrogenase is a membrane-bound

cytochrome b Cytochrome b within both molecular and cell biology, is a protein found in the mitochondria of eukaryotic cells. It functions as part of the electron transport chain and is the main subunit of transmembrane cytochrome bc1 and b6f complexes. F ...

consisting of four transmembrane helices and two heme b groups which produce a four-helix bundle which aids in heme binding. The heme b cofactors bound to the gamma subunit allow for the hopping of electrons through the subunit. The transmembrane helices maintain both heme b groups, while only three provide the heme ligands thereby anchoring Fe-heme. The periplasmic heme b group accepts electrons from Fe-4S3 clusters of the β-subunit’s periplasmic domain. The cytoplasmic heme b group accepts electrons from the periplasmic heme b group, where electron flow is then directed towards the menaquinone (vitamin K) reduction site, present in the transmembrane domain of the gamma subunit. The menaquinone reduction site in the γ-subunit, accepts electrons through the binding of a histidine ligand of the cytoplasmic heme b. Colored_electron_tunneling_F-DHN

Additional reading

References

10.Siegbahn, P. E. M. (2022, February 22). ''Energetics for CO2 reduction by molybdenum-containing formate ...'' ACS Publications. Retrieved December 5, 2022, from https://pubs.acs.org/doi/10.1021/acs.jpcb.2c00151 11.Maia, L. B., & Fonseca, L. (2016, June 27). ''Reduction of Carbon Dioxide by a Molybdenum-Containing Formate Dehydrogenase: A Kinetic and Mechanistic Study''. Retrieved December 5, 2022, from https://pubs.acs.org/doi/10.1021/jacs.6b03941

External links