Ferredoxin NADP+ Reductase

Ferredoxin 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 Function

In many facultatively anaerobic bacteria, this protein acts as an oxygen sensor modifying gene expression that adapts the cell to anaerobic growth. The activity of FNR regulates the cells ability to metabolize aerobically or anaerobically so that when oxygen is abundant, FNR is destabilized and converted into an inactive form. The protein is activated when there are low oxygen tensions. This function is known as transcriptional sensor-regulation. 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 it is abundant. This is a reversibly constitutive regulation pathway. 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 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.

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 hot due to these differences.^[1]

Structural highlights

In 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

References

1. ↑ 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

Constantinidou, Chrystala, Jon L. Hobman, Lesley Griffiths, Mala D. Patel, Charles W. Penn, Jeffrey A. Cole, and Tim W. Overton. “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.” Journal of Biological Chemistry 281, no. 8 (February 24, 2006): 4802–15. ^[2]