Ferredoxin NADP+ Reductase: Difference between revisions
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==Overview== | ==Overview== | ||
<StructureSection load='4FK8' size='340' side='right' caption='FNR protein' scene=''> | [[Image:Ironsulfurferredoxin.png|400px|left|thumb| Ferredoxin NADP<sup>+</sup> Reductase zoomed in (4FK8)]] | ||
<StructureSection load='4FK8' size='340' frame='true' side='right' caption='FNR protein containg FAD (PDB code [[4fk8]])' scene=''> | |||
==Function== | |||
'''Ferredoxin NADP<sup>+</sup> reductase''' [http://en.wikipedia.org/wiki/Ferredoxin—NADP(%2B)_reductase] is an enzyme that catalyzes the reduction of NADP<sup>+</sup> to NADPH. This enzyme belongs to a family of enzymes called oxidoreductases[http://en.wikipedia.org/wiki/Oxidoreductase] that contain iron-sulfur proteins as electron donors and NAD<sup>+</sup> or NADP<sup>+</sup> as electron acceptors. FAD, [flavin adenine dinucleotide][http://en.wikipedia.org/wiki/Flavin_adenine_dinucleotide], is also a cofactor of FNR. The ferredoxin NADP<sup>+</sup> reductase participates in a general reaction that proceeds as follows: | '''Ferredoxin NADP<sup>+</sup> reductase''' [http://en.wikipedia.org/wiki/Ferredoxin—NADP(%2B)_reductase] is an enzyme that catalyzes the reduction of NADP<sup>+</sup> to NADPH. This enzyme belongs to a family of enzymes called oxidoreductases[http://en.wikipedia.org/wiki/Oxidoreductase] that contain iron-sulfur proteins as electron donors and NAD<sup>+</sup> or NADP<sup>+</sup> as electron acceptors. FAD, [flavin adenine dinucleotide][http://en.wikipedia.org/wiki/Flavin_adenine_dinucleotide], is also a cofactor of FNR. The ferredoxin NADP<sup>+</sup> reductase participates in a general reaction that proceeds as follows: | ||
2 reduced ferredoxin + NADP<sup>+</sup> ---> H<sup>+</sup> + 2 oxidized ferredoxin + NADPH | '''2 reduced ferredoxin + NADP<sup>+</sup> ---> H<sup>+</sup> + 2 oxidized ferredoxin + NADPH'''[http://en.wikipedia.org/wiki/Ferredoxin—NADP(%2B)_reductase] | ||
== Anaerobic Function == | ==Anaerobic Function== | ||
In many facultatively anaerobic bacteria, | In many facultatively anaerobic bacteria, FNR acts as an oxygen sensor modifying gene expression that adapts the cell to anaerobic growth. The activity of FNR regulates the cell's ability to metabolize aerobically or anaerobically so that when oxygen is abundant, FNR is destabilized and converted into an inactive form.<ref> PMID: 3036034 </ref> FNR is activated when there are low oxygen tensions (hypoxia). This function is known as transcriptional sensor-regulation.<ref> PMID: 7747938</ref> The predominant pathway in which this regulation occurs is through binding or oxidation-reduction of oxygen in the iron sulfur center, in which the iron serves as the initiating cofactor that interacts with the oxygen when oxygen is abundant. This is a reversibly constitutive regulation pathway.<ref> PMID: 16377617 </ref> | ||
Although facultative anaerobes prefer to use molecular oxygen as the terminal electron acceptor due the high reduction potential, low oxygen stress is able to induce the bacteria to use FNR instead. The transformation involves other proteins such as the sensor regulator system ArcAB, however these regulators are affected by other intermediates. FNR combines the functions of both a sensor and a regulator. | Although facultative anaerobes prefer to use molecular oxygen as the terminal electron acceptor due the high reduction potential, low oxygen stress is able to induce the bacteria to use FNR instead. The transformation involves other proteins such as the sensor regulator system ArcAB, however these regulators are affected by other intermediates. FNR combines the functions of both a sensor and a regulator. | ||
FNR is also an active protein in plants, and is found in the chloroplast and thylakoid membrane of the cell. The FNR reductive mechanism is responsible for the transfer of the final electrons during photosynthesis from photosystem I to NADPH, which then goes on to participate the Calvin cycle as a reducing cofactor. | ==Other Functions== | ||
FNR is also an active protein in plants, and is found in the chloroplast and thylakoid membrane of the cell. The FNR reductive mechanism is responsible for the transfer of the final electrons during photosynthesis from photosystem I to NADPH, which then goes on to participate the [[Calvin cycle]] as a reducing cofactor. | |||
In other organisms, FNR plays a role in metabolism such as oxidative stress response and steroid metabolism.[http://en.wikipedia.org/wiki/Ferredoxin—NADP(%2B)_reductase] | |||
==Relevance== | |||
Observing the role of FNR in bacteria has the potential to be very important in the realm of pathogenic bacterial drug resistance. Understanding the mechanism and differences of the FNR function in organisms could be essential in the development of antimicrobial. Because the FNR mechanism and protein itself is slightly different in most living organisms, researchers are interested in learning how the FNR function can be inhibited specifically for harmful pathogens as this would likely not affect the host due to these differences and could be an antibiotic inhibition mechanism.<ref>PMID:23382856</ref> | |||
== Structural highlights == | == Structural highlights == | ||
In its active form, the protein is a <scene name='69/699901/Dimeric_fnr/1'>dimer</scene> and contains a [4Fe-4S]<sup>+2</sup> cluster. When inactive, the protein is monomeric and containts a [3Fe-4S]<sup>+2</sup> cluster. FNR in its <scene name='69/699901/Monomeric_fnr/1'>monomer</scene> form can be seen here, with bound NADP and FAD | In its active form, the protein is a <scene name='69/699901/Dimeric_fnr/1'>dimer</scene> and contains a [4Fe-4S]<sup>+2</sup> cluster. When inactive, the protein is monomeric and containts a [3Fe-4S]<sup>+2</sup> cluster. FNR in its <scene name='69/699901/Monomeric_fnr/1'>monomer</scene> form can be seen here, with bound NADP and FAD.<ref> PMID: 21166900 </ref> | ||
== | == 3D Structures of Ferredoxin NADP+ reductase == | ||
[[Ferredoxin NADP+ Reductase 3D structures]] | |||
</StructureSection> | |||
== References == | |||
<references/> | |||
[[Category:Topic Page]] | |||
Latest revision as of 13:58, 2 January 2023
OverviewOverview
FunctionFerredoxin NADP+ reductase [1] is an enzyme that catalyzes the reduction of NADP+ to NADPH. This enzyme belongs to a family of enzymes called oxidoreductases[2] that contain iron-sulfur proteins as electron donors and NAD+ or NADP+ as electron acceptors. FAD, [flavin adenine dinucleotide][3], is also a cofactor of FNR. The ferredoxin NADP+ reductase participates in a general reaction that proceeds as follows: 2 reduced ferredoxin + NADP+ ---> H+ + 2 oxidized ferredoxin + NADPH[4] Anaerobic FunctionIn many facultatively anaerobic bacteria, FNR acts as an oxygen sensor modifying gene expression that adapts the cell to anaerobic growth. The activity of FNR regulates the cell's ability to metabolize aerobically or anaerobically so that when oxygen is abundant, FNR is destabilized and converted into an inactive form.[1] FNR is activated when there are low oxygen tensions (hypoxia). This function is known as transcriptional sensor-regulation.[2] The predominant pathway in which this regulation occurs is through binding or oxidation-reduction of oxygen in the iron sulfur center, in which the iron serves as the initiating cofactor that interacts with the oxygen when oxygen is abundant. This is a reversibly constitutive regulation pathway.[3] Although facultative anaerobes prefer to use molecular oxygen as the terminal electron acceptor due the high reduction potential, low oxygen stress is able to induce the bacteria to use FNR instead. The transformation involves other proteins such as the sensor regulator system ArcAB, however these regulators are affected by other intermediates. FNR combines the functions of both a sensor and a regulator. Other FunctionsFNR is also an active protein in plants, and is found in the chloroplast and thylakoid membrane of the cell. The FNR reductive mechanism is responsible for the transfer of the final electrons during photosynthesis from photosystem I to NADPH, which then goes on to participate the Calvin cycle as a reducing cofactor. In other organisms, FNR plays a role in metabolism such as oxidative stress response and steroid metabolism.[5] RelevanceObserving the role of FNR in bacteria has the potential to be very important in the realm of pathogenic bacterial drug resistance. Understanding the mechanism and differences of the FNR function in organisms could be essential in the development of antimicrobial. Because the FNR mechanism and protein itself is slightly different in most living organisms, researchers are interested in learning how the FNR function can be inhibited specifically for harmful pathogens as this would likely not affect the host due to these differences and could be an antibiotic inhibition mechanism.[4] Structural highlightsIn its active form, the protein is a and contains a [4Fe-4S]+2 cluster. When inactive, the protein is monomeric and containts a [3Fe-4S]+2 cluster. FNR in its form can be seen here, with bound NADP and FAD.[5] 3D Structures of Ferredoxin NADP+ reductaseFerredoxin NADP+ Reductase 3D structures
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ReferencesReferences
- ↑ Unden G, Duchene A. On the role of cyclic AMP and the Fnr protein in Escherichia coli growing anaerobically. Arch Microbiol. 1987 Mar;147(2):195-200. PMID:3036034
- ↑ Unden G, Becker S, Bongaerts J, Schirawski J, Six S. Oxygen regulated gene expression in facultatively anaerobic bacteria. Antonie Van Leeuwenhoek. 1994;66(1-3):3-22. PMID:7747938
- ↑ Constantinidou C, Hobman JL, Griffiths L, Patel MD, Penn CW, Cole JA, Overton TW. A reassessment of the FNR regulon and transcriptomic analysis of the effects of nitrate, nitrite, NarXL, and NarQP as Escherichia coli K12 adapts from aerobic to anaerobic growth. J Biol Chem. 2006 Feb 24;281(8):4802-15. Epub 2005 Dec 22. PMID:16377617 doi:http://dx.doi.org/10.1074/jbc.M512312200
- ↑ Baugh L, Gallagher LA, Patrapuvich R, Clifton MC, Gardberg AS, Edwards TE, Armour B, Begley DW, Dieterich SH, Dranow DM, Abendroth J, Fairman JW, Fox D 3rd, Staker BL, Phan I, Gillespie A, Choi R, Nakazawa-Hewitt S, Nguyen MT, Napuli A, Barrett L, Buchko GW, Stacy R, Myler PJ, Stewart LJ, Manoil C, Van Voorhis WC. Combining functional and structural genomics to sample the essential Burkholderia structome. PLoS One. 2013;8(1):e53851. doi: 10.1371/journal.pone.0053851. Epub 2013 Jan 31. PMID:23382856 doi:http://dx.doi.org/10.1371/journal.pone.0053851
- ↑ Tolla DA, Savageau MA. Phenotypic repertoire of the FNR regulatory network in Escherichia coli. Mol Microbiol. 2011 Jan;79(1):149-65. doi: 10.1111/j.1365-2958.2010.07437.x. Epub, 2010 Nov 8. PMID:21166900 doi:http://dx.doi.org/10.1111/j.1365-2958.2010.07437.x