Formate dehydrogenases are a set of

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

s that catalyse the oxidation of

formate Formate (IUPAC name: methanoate) is the conjugate base of formic acid. Formate is an anion () or its derivatives such as ester of formic acid. The salts and esters are generally colorless. Fundamentals When dissolved in water, formic acid co ...

carbon dioxide Carbon dioxide is a chemical compound with the chemical formula . It is made up of molecules that each have one carbon atom covalent bond, covalently double bonded to two oxygen atoms. It is found in a gas state at room temperature and at norma ...

, 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 iron (Fe) atom at its core, as a cofactor. They are involved in the electron transport chain and redox catalysis. They are classified according to the type of heme and its ...

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 Present-day climate change includes both global warming—the ongoing increase in global average temperature—and its wider effects on Earth's climate system. Climate change in a broader sense also includes previous long-term changes ...

Function

NAD-dependent formate dehydrogenases are important in methylotrophic

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

and

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

, being vital in the catabolism of C1 compounds such as

methanol Methanol (also called methyl alcohol and wood spirit, amongst other names) is an organic chemical compound and the simplest aliphatic Alcohol (chemistry), alcohol, with the chemical formula (a methyl group linked to a hydroxyl group, often ab ...

. The cytochrome-dependent enzymes are more important in anaerobic metabolism in prokaryotes. For example, in ''

E. coli ''Escherichia coli'' ( )Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escherichia'' that is commonly foun ...

'', 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 Oxidoreductase, reductase under anaerobic conditions in some bacteria, with DMSO b ...

, 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: Molybdopte ...

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 along with 1,2-diselenolene derivatives, are unsaturated bidentate ligand wherein the two dono ...

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.,

). A popular mechanistic proposal entails transfer of H⁻ from formate to the Mo/W^VI=S group.

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 is a protein found in the membranes of aerobic cells. In eukaryotic mitochondria (inner membrane) and in aerobic prokaryotes, cytochrome b is a component of respiratory chain complex III () — also known as the bc1 complex or ubiq ...

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

External links