Biology:Ferric-chelate reductase
| ferric-chelate reductase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| EC number | 1.16.1.7 | ||||||||
| CAS number | 122097-10-3 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| Gene Ontology | AmiGO / QuickGO | ||||||||
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In enzymology, a ferric-chelate reductase (EC 1.16.1.7) is an enzyme that catalyzes the chemical reaction
- 2 Fe(II) + NAD+ [math]\displaystyle{ \rightleftharpoons }[/math] 2 Fe(III) + NADH + H+
Thus, the two substrates of this enzyme are Fe(II) and NAD+, whereas its 3 products are Fe(III), NADH, and H+.
Nomenclature
This enzyme belongs to the family of oxidoreductases, specifically those oxidizing metal ion with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is Fe(II):NAD+ oxidoreductase. Other names in common use include:
- ferric chelate reductase
- iron chelate reductase
- NADH:Fe3+-EDTA reductase
- NADH2:Fe3+ oxidoreductase
Prokaryotes
Most studied ferric reductases in bacteria are either specific for a ferric iron complex or non-specific flavin ferric reductases, with the latter being more common in bacteria.[1] Both reductase forms are suitable complimentary soluble pathways for the efficient extraction of iron via siderophores.[1]
Bacterial soluble flavin reductase in E. coli
Non-specific bacterial flavin reductase has been well researched within E. coli, which is the NAD(P)H: flavin oxidoreductase (Fre).[1] In E. coli, NAD(P)H is reduced to either free FAD or riboflavin, which is known to reduce ferric iron to ferrous iron intracellularly. Fre is also structurally similar to ferredoxin-NADP+ reductase (Fpr), and bids flavin cofactor to reduce ferredoxin and siderophore bound ferric iron.[2] Despite these hypothesized structural commonalities, not much is known regarding this enzymatic structure overall.
Bacterial flavin reductase in Paracoccus denitrificans
Paracoccus denitrificans contains two enzymes which aid in iron reduction - ferric reductase A and B (FerA and FerB).[3] FerA binds to oxidized flavins (FMN and FAD).[3] Unlike the many structural unknowns surrounding Fre, the crystal structure of FerA is well defined (see Fig. 6 in Sedlácek et. al., 2016). FerA consists of two protein subunits, with three alpha-helices and ten beta-sheets total.[3]
Archaeal soluble flavin reductase in Archaeoglobus fulgidus
Archaeoglobus fulgidus has been shown to have a similar ferric reductase (FeR) to the NAD(P)H:flavin oxidoreductase family.[1] FeR is archaea specific and reduces external, synthetic ferric iron complexes and Fe(III)-citrate with NAD(P)H and bound flavin adenine dinucleotide (FAD) or flavin mononucleotide (FMN) cofactor.[4]
Eukaryotes
Soluble ferric reductase in yeast
Ferric reductases are present in some unicellular eukaryotes, including pathogenic yeast which utilize ferric reductases during infection of a host.[5][6] Contrary to archaea and bacteria, soluble ferric reductases are much more rare in fungi, with more research necessary to determine just how widespread soluble ferric reductase are amongst fungi.[1] These soluble ferric reductases in fungi are known to operate extracellularly, as fungi are capable of excreting them to reduce iron in the environment.[1] This mechanism of ferric reductase excretion allows the labilization of iron in the environment, and typically happens concurrently with fungal siderophore pathways and iron reduction on cellular surfaces, which occur with membrane-bound ferric reductases.[1]
Membrane-bound ferric reductase in yeast
Membrane-bound ferric reductases are fore more common in yeast cells relative to soluble ferric reductases. These reductases utilize NAD(P)H, falvin, and heme b cofactors in order to move reducing agents across their membranes to an extracellular Fe(III) source.[5][6] After this, the reduced Fe(II) may be re-oxidized and rebound to be transported across the membrane again via both Cu-dependent ferroxidase and Fe(III) transport proteins.[6][7] Alternatively, ferrous, unchelated iron can be transported via low-affinity proteins, however, this mechanism is less common than the former.[6]
Membrane-bound ferric reductase in Arabidopsis
Most plants contain ferric-chelate reductase in order to uptake iron from the environment. Arabidopsis is capable of increasing the activity of ferric-chelate reductase, which is located in the membranes of root epidermal cells, in environments with limited iron availability.[8] Additionally, it is hypothesized that the activity of this reductase stimulates iron release from organic compounds within the soils, releasing it for biological uptake.[9] The crystalline structure of this enzyme in Arabidopsis has not yet been well constrained, however, it is hypothesized that, due to its similar functions, its structure is likely similar to ferric-chelate reductases in both yeast and human phagocytic NADPH oxidase gp91phox.[10][11]
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 "Ferric iron reductases and their contribution to unicellular ferrous iron uptake". Journal of Inorganic Biochemistry 218: 111407. May 2021. doi:10.1016/j.jinorgbio.2021.111407. PMID 33684686.
- ↑ "Ferredoxin-NADP+ reductase from Pseudomonas putida functions as a ferric reductase". Journal of Bacteriology 191 (5): 1472–1479. March 2009. doi:10.1128/JB.01473-08. PMID 19114475.
- ↑ 3.0 3.1 3.2 "Biochemical properties and crystal structure of the flavin reductase FerA from Paracoccus denitrificans". Microbiological Research 188-189: 9–22. 2016-07-01. doi:10.1016/j.micres.2016.04.006. PMID 27296958.
- ↑ "Identification and characterization of a novel ferric reductase from the hyperthermophilic Archaeon Archaeoglobus fulgidus". The Journal of Biological Chemistry 274 (51): 36715–36721. December 1999. doi:10.1074/jbc.274.51.36715. PMID 10593977.
- ↑ 5.0 5.1 "Role of ferric reductases in iron acquisition and virulence in the fungal pathogen Cryptococcus neoformans". Infection and Immunity 82 (2): 839–850. February 2014. doi:10.1128/IAI.01357-13. PMID 24478097.
- ↑ 6.0 6.1 6.2 6.3 "Adaptation to iron deficiency in human pathogenic fungi". Biochimica et Biophysica Acta. Molecular Cell Research 1867 (10): 118797. October 2020. doi:10.1016/j.bbamcr.2020.118797. PMID 32663505.
- ↑ "The metalloreductase Fre6p in Fe-efflux from the yeast vacuole". The Journal of Biological Chemistry 282 (39): 28619–28626. September 2007. doi:10.1074/jbc.M703398200. PMID 17681937.
- ↑ "A ferric-chelate reductase for iron uptake from soils". Nature 397 (6721): 694–697. February 1999. doi:10.1038/17800. PMID 10067892. Bibcode: 1999Natur.397..694R.
- ↑ "The Molecular Biology of Iron and Zinc Uptake in Saccharomyces cerevisiae". Metal Ions in Gene Regulation. Boston, MA: Springer US. 1998. pp. 342–371. doi:10.1007/978-1-4615-5993-1_13. ISBN 978-1-4613-7745-0.
- ↑ "Genetic evidence that ferric reductase is required for iron uptake in Saccharomyces cerevisiae". Molecular and Cellular Biology 10 (5): 2294–2301. May 1990. doi:10.1128/mcb.10.5.2294. PMID 2183029.
- ↑ "The respiratory burst oxidase". The Journal of Biological Chemistry 269 (40): 24519–24522. October 1994. doi:10.1016/s0021-9258(17)31418-7. PMID 7929117.
Further reading
- "Localization of donor and acceptor sites of NADH dehydrogenase activities using inside-out and right-side-out plasma membrane vesicles from plants". FEBS Lett. 239: 23–28. 1988. doi:10.1016/0014-5793(88)80538-6. http://urn.kb.se/resolve?urn=urn:nbn:se:hj:diva-3869.
- "MIA-QSAR modelling of anti-HIV-1 activities of some 2-amino-6-arylsulfonylbenzonitriles and their thio and sulfinyl congeners". Organic & Biomolecular Chemistry 4 (6): 1154–1159. March 2006. doi:10.1039/b516396j. PMID 16525561.
- "Pyridine nucleotide-dependent ferricyanide reduction associated with isolated plasma membranes of maize (Zea mays L.) roots". Protoplasma 135 (2–3): 144–154. 1986. doi:10.1007/BF01277007. https://naldc-legacy.nal.usda.gov/naldc/download.xhtml?id=19193&content=PDF.
- "Redox reactions of plasma membranes isolated from soybean hypocotyls by phase partition". Plant Sci. 48: 1–10. 1986. doi:10.1016/0168-9452(87)90062-8.
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