Formate dehydrogenase

Last updated
Formate dehydrogenase N, transmembrane
1kqg.jpg
Formate dehydrogenase-N hetero9mer, E.Coli
Identifiers
SymbolForm-deh_trans
Pfam PF09163
InterPro IPR015246
SCOP2 1kqf / SCOPe / SUPFAM
OPM superfamily 3
OPM protein 1kqf
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary
PDB 1kqf B:246-289 1kqg B:246-289

Formate dehydrogenases are a set of enzymes that catalyse the oxidation of formate to carbon dioxide, donating the electrons to a second substrate, such as NAD+ in formate:NAD+ oxidoreductase (EC 1.17.1.9) or to a cytochrome in formate:ferricytochrome-b1 oxidoreductase (EC 1.2.2.1). [1] This family of enzymes has attracted attention as inspiration or guidance on methods for the carbon dioxide fixation, relevant to global warming. [2]

Contents

Function

NAD-dependent formate dehydrogenases are important in methylotrophic yeast and bacteria, being vital in the catabolism of C1 compounds such as methanol. [3] The cytochrome-dependent enzymes are more important in anaerobic metabolism in prokaryotes. [4] 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. [5] [6]

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, with two molybdopterin cofactors bound to Mo/W in a bidentate fashion. The fifth and sixth ligands are sulfide and either cysteinate or selenocysteinate. [7]

The mechanism of action appears to involve 2e redox of the metal centers, induced by hydride transfer from formate and release of carbon dioxide:

S=MVI(Scys)(SR)4 + HCO−2 ⇌ HS−MIV(Scys)(SR)4 + CO2
S=MVI(Secys)(SR)4 + HCO−2 ⇌ HS−MIV(Secys)(SR)4 + CO2

In this scheme, (SR)4 represents the four thiolate-like ligands provided by the two dithiolene cofactors, the molybdopterins. 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/WVI=S group. [8]

Formate Dehydrogenase (PDB 1KQF, 1.6 A resolution, from E. coli); overall view of the electron transport chain showing the [Fe4S4] clusters in the periplasmic alpha and beta subunits, and the cytoplasmic gamma subunit showing the Fe(heme b)P and the Fe-(heme b)C menoquinone binding site where an HQNO ligand is bound close the Fe(heme b)C. Atom colours: Fe = orange, S = yellow, C = grey, O = red, N = blue. Formate Dehydrogenase 1kqf overall protein 1 (KC).png
Formate Dehydrogenase (PDB 1KQF, 1.6 A resolution, from E. coli); overall view of the electron transport chain showing the [Fe4S4] clusters in the periplasmic alpha and beta subunits, and the cytoplasmic gamma subunit showing the Fe(heme b)P and the Fe-(heme b)C menoquinone binding site where an HQNO ligand is bound close the Fe(heme b)C. Atom colours: Fe = orange, S = yellow, C = grey, O = red, N = blue.

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 [4Fe-4S] ferredoxin clusters. The judicious alignment of the [4Fe-4S] clusters in a chain through the subunit have low separation distances, which allow rapid electron flow through [4Fe-4S]-1, [4Fe-4S]-4, [4Fe-4S]-2, and [4Fe-4S]-3 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 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 [4Fe-4S]-3 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. [9]

Menaquinone binding site alongside proposed water proton pathway Colored electron tunneling F-DHN.jpg
Menaquinone binding site alongside proposed water proton pathway

See also

Additional reading

Related Research Articles

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References

  1. ↑ Hille, Russ; Hall, James; Basu, Partha (2014). "The Mononuclear Molybdenum Enzymes". Chemical Reviews. 114 (7): 3963–4038. doi:10.1021/cr400443z. PMC   4080432 . PMID   24467397.
  2. ↑ Amao, Yutaka (2018). "Formate dehydrogenase for CO2 utilization and its application". Journal of CO2 Utilization. 26: 623–641. doi: 10.1016/j.jcou.2018.06.022 . S2CID   189383769.
  3. ↑ Popov VO, Lamzin VS (1994). "NAD(+)-dependent formate dehydrogenase". Biochem. J. 301 (3): 625–43. doi:10.1042/bj3010625. PMC   1137035 . PMID   8053888.
  4. ↑ Jormakka M, Byrne B, Iwata S (2003). "Formate dehydrogenase--a versatile enzyme in changing environments". Curr. Opin. Struct. Biol. 13 (4): 418–23. doi:10.1016/S0959-440X(03)00098-8. PMID   12948771.
  5. ↑ Graham A, Boxer DH (1981). "The organization of formate dehydrogenase in the cytoplasmic membrane of Escherichia coli". Biochem. J. 195 (3): 627–37. doi:10.1042/bj1950627. PMC   1162934 . PMID   7032506.
  6. ↑ Ruiz-Herrera J, DeMoss JA (1969). "Nitrate reductase complex of Escherichia coli K-12: participation of specific formate dehydrogenase and cytochrome b1 components in nitrate reduction". J. Bacteriol. 99 (3): 720–9. doi:10.1128/JB.99.3.720-729.1969. PMC   250087 . PMID   4905536.
  7. ↑ Stripp, Sven T.; Duffus, Benjamin R.; Fourmond, Vincent; Léger, Christophe; Leimkühler, Silke; Hirota, Shun; Hu, Yilin; Jasniewski, Andrew; Ogata, Hideaki; Ribbe, Markus W. (2022). "Second and Outer Coordination Sphere Effects in Nitrogenase, Hydrogenase, Formate Dehydrogenase, and CO Dehydrogenase". Chemical Reviews. 122 (14): 11900–11973. doi:10.1021/acs.chemrev.1c00914. PMC   9549741 . PMID   35849738.
  8. ↑ Fogeron, Thibault; Li, Yun; Fontecave, Marc (2022). "Formate Dehydrogenase Mimics as Catalysts for Carbon Dioxide Reduction". Molecules. 27 (18): 5989. doi: 10.3390/molecules27185989 . PMC   9506188 . PMID   36144724.
  9. ↑ Stiefel, Edward (2002-03-31). "Faculty Opinions recommendation of Molecular basis of proton motive force generation: structure of formate dehydrogenase-N". doi: 10.3410/f.1004770.61154 .{{cite journal}}: Cite journal requires |journal= (help)
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