Ferredoxin reductase (FNR), an FAD and NAD(P) binding protein, was intially identified as a chloroplast reductase activity, catalyzing the electron transfer from reduced iron-sulfur protein ferredoxin to NADP+ as the final step in the electron transport mechanism of photosystem I. FNR transfers electrons from reduced ferredoxin to FAD (forming FADH2 via a semiquinone intermediate) and then transfers a hydride ion to convert NADP+ to NADPH. FNR has since been shown to utilize a variety of electron acceptors and donors and has a variety of physiological functions including nitrogen assimilation, dinitrogen fixation, steroid hydroxylation, fatty acid metabolism, oxygenase activity, and methane assimilation in many organisms. FNR has an NAD(P)-binding sub-domain of the alpha/beta class and a discrete (usually N-terminal) flavin sub-domain which vary in orientation with respect to the NAD(P) binding domain. The N-terminal moeity may contain a flavin prosthetic group (as in flavoenzymes) or use flavin as a substrate. Because flavins such as FAD can exist in oxidized, semiquinone (one- electron reduced), or fully reduced hydroquinone forms, FNR can interact with one and 2 electron carriers. FNR has a strong preference for NADP(H) vs NAD(H).

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 40067426   3 KGKFAIRPDKKsnpiirtVKSVGTIAGGTGITPMLQVIRAIMKDPDDHTVCHLLFANQ 60
Cdd:cd06183  93 FGKFEYKPNGK-------VKHIGMIAGGTGITPMLQLIRAILKDPEDKTKISLLYANR 143

Cytochrome b5 reductase catalyzes the reduction of 2 molecules of cytochrome b5 using NADH as an electron donor. Like ferredoxin reductases, these proteins have an N-terminal FAD binding subdomain and a C-terminal NADH binding subdomain, separated by a cleft, which accepts FAD. The NADH-binding moiety interacts with part of the FAD and resembles a Rossmann fold. However, NAD is bound differently than in canonical Rossmann fold proteins. Nitrate reductases, flavoproteins similar to pyridine nucleotide cytochrome reductases, catalyze the reduction of nitrate to nitrite. The enzyme can be divided into three functional fragments that bind the cofactors molybdopterin, heme-iron, and FAD/NADH.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 40067426   3 KGKFAIRPDKKsnpiirtVKSVGTIAGGTGITPMLQVIRAIMKDPDDHTVCHLLFANQ 60
Cdd:cd06183  93 FGKFEYKPNGK-------VKHIGMIAGGTGITPMLQLIRAILKDPEDKTKISLLYANR 143

Oxidoreductase NAD-binding domain; Xanthine dehydrogenases, that also bind FAD/NAD, have essentially no similarity.

                          10        20        30
                  ....*....|....*....|....*....|....
gi 40067426    27 IAGGTGITPMLQVIRAIMKDPDDHTVCHLLFANQ 60
Cdd:pfam00175   2 IAGGTGIAPVRSMLRAILEDPKDPTQVVLVFGNR 35

Cytochrome b5 reductase catalyzes the reduction of 2 molecules of cytochrome b5 using NADH as an electron donor. Like ferredoxin reductases, these proteins have an N-terminal FAD binding subdomain and a C-terminal NADH binding subdomain, separated by a cleft, which accepts FAD. The NADH-binding moiety interacts with part of the FAD and resembles a Rossmann fold. However, NAD is bound differently than in canonical Rossmann fold proteins. Nitrate reductases, flavoproteins similar to pyridine nucleotide cytochrome reductases, catalyze the reduction of nitrate to nitrite. The enzyme can be divided into three functional fragments that bind the cofactors molybdopterin, heme-iron, and FAD/NADH.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 40067426   3 KGKFAIRPDKKsnpiirtVKSVGTIAGGTGITPMLQVIRAIMKDPDDHTVCHLLFANQ 60
Cdd:cd06183  93 FGKFEYKPNGK-------VKHIGMIAGGTGITPMLQLIRAILKDPEDKTKISLLYANR 143

NADH-cytochrome B5 reductase; Provisional

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 40067426    2 GKGKFAIRPDKKSnPIIRTVKSVGTIAGGTGITPMLQVIRAIMKDPDDHTVCHLLFANQ 60
Cdd:PTZ00319 148 GNGTYTVHKGKGG-LKTMHVDAFAMIAGGTGITPMLQIIHAIKKNKEDRTKVFLVYANQ 205

cytochrome b5 reductase; Provisional

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 40067426   22 KSVGTIAGGTGITPMLQVIR-AIMKDPD----DHTVCHLLFANQ 60
Cdd:PTZ00274 160 KHVGMIAGGTGFTPMLQIIRhSLTEPWDsgevDRTKLSFLFCNR 203

Ferredoxin reductase (FNR), an FAD and NAD(P) binding protein, was intially identified as a chloroplast reductase activity, catalyzing the electron transfer from reduced iron-sulfur protein ferredoxin to NADP+ as the final step in the electron transport mechanism of photosystem I. FNR transfers electrons from reduced ferredoxin to FAD (forming FADH2 via a semiquinone intermediate) and then transfers a hydride ion to convert NADP+ to NADPH. FNR has since been shown to utilize a variety of electron acceptors and donors and has a variety of physiological functions including nitrogen assimilation, dinitrogen fixation, steroid hydroxylation, fatty acid metabolism, oxygenase activity, and methane assimilation in many organisms. FNR has an NAD(P)-binding sub-domain of the alpha/beta class and a discrete (usually N-terminal) flavin sub-domain which vary in orientation with respect to the NAD(P) binding domain. The N-terminal moeity may contain a flavin prosthetic group (as in flavoenzymes) or use flavin as a substrate. Because flavins such as FAD can exist in oxidized, semiquinone (one- electron reduced), or fully reduced hydroquinone forms, FNR can interact with one and 2 electron carriers. FNR has a strong preference for NADP(H) vs NAD(H).

                        10        20        30
                ....*....|....*....|....*....|....
gi 40067426  27 IAGGTGITPMLQVIRAIMKDPDDHTVcHLLFANQ 60
Cdd:cd00322 103 IAGGIGITPFRSMLRHLAADKPGGEI-TLLYGAR 135

Predicted ferric reductase [Inorganic ion transport and metabolism];

                        10        20        30
                ....*....|....*....|....*....|...
gi 40067426  27 IAGGTGITPMLQVIRAIMKDPDDHTVCHLLFAN 59
Cdd:COG4097 324 IAGGIGITPFLALLRALAARPGDQRPVDLFYCV 356

Ferredoxin reductase-like proteins catalyze electron transfer between an NAD(P)-binding domain of the alpha/beta class and a discrete (usually N-terminal) domain which varies in orientation with respect to the NAD(P) binding domain. The N-terminal region may contain a flavin prosthetic group (as in flavoenzymes) or use flavin as a substrate. Ferredoxin is reduced in the final stage of photosystem I. The flavoprotein Ferredoxin-NADP+ reductase transfers electrons from reduced ferredoxin to FAD (forming FADH2 via a semiquinone intermediate) which then transfers a hydride ion to convert NADP+ to NADPH.

                        10        20        30
                ....*....|....*....|....*....|....*.
gi 40067426  27 IAGGTGITPMLQVIRAIMKDP--DDHtvcHLLFANQ 60
Cdd:cd06196 105 IAGGAGITPFIAILRDLAAKGklEGN---TLIFANK 137

Flavodoxin/ferredoxin--NADP reductase [Energy production and conversion];

                        10        20        30
                ....*....|....*....|....*....|....
gi 40067426  27 IAGGTGITPMLQVIRAIMKDPDDHTVcHLLFANQ 60
Cdd:COG1018 114 IAGGIGITPFLSMLRTLLARGPFRPV-TLVYGAR 146

Iron-sulfur binding ferredoxin reductase (FNR) proteins combine the FAD and NAD(P) binding regions of FNR with an iron-sulfur binding cluster domain. Ferredoxin-NADP+ (oxido)reductase is an FAD-containing enzyme that catalyzes the reversible electron transfer between NADP(H) and electron carrier proteins such as ferredoxin and flavodoxin. Isoforms of these flavoproteins (i.e. having a non-covalently bound FAD as a prosthetic group) are present in chloroplasts, mitochondria, and bacteria in which they participate in a wide variety of redox metabolic pathways. The C-terminal domain contains most of the NADP(H) binding residues and the N-terminal domain interacts non-covalently with the isoalloxazine rings of the flavin molecule which lies largely in a large gap between the two domains. Ferredoxin-NADP+ reductase first accepts one electron from reduced ferredoxin to form a flavin semiquinone intermediate. The enzyme then accepts a second electron to form FADH2 which then transfers two electrons and a proton to NADP+ to form NADPH.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 40067426   4 GKFAIRPdkksnpiiRTVKSVGTIAGGTGITPMLQVIRAImKDPDDHTVCHLLFANQ 60
Cdd:cd06217  98 GTFTWNP--------LHGDPVVLLAGGSGIVPLMSMIRYR-RDLGWPVPFRLLYSAR 145

FAD/NAD(P) binding domain of ferredoxin reductase-like proteins. Ferredoxin reductase (FNR) was intially identified as a chloroplast reductase activity, catalyzing the electron transfer from reduced iron-sulfur protein ferredoxin to NADP+ as the final step in the electron transport mechanism of photosystem I. FNR transfers electrons from reduced ferredoxin to FAD (forming FADH2 via a semiquinone intermediate) and then transfers a hydride ion to convert NADP+ to NADPH. FNR has since been shown to utilize a variety of electron acceptors and donors and have a variety of physiological functions in a variety of organisms including nitrogen assimilation, dinitrogen fixation, steroid hydroxylation, fatty acid metabolism, oxygenase activity, and methane assimilation. FNR has an NAD(P)-binding sub-domain of the alpha/beta class and a discrete (usually N-terminal) flavin sub-domain which varies in orientation with respect to the NAD(P) binding domain. The N-terminal moeity may contain a flavin prosthetic group (as in flavoenzymes) or use flavin as a substrate. Because flavins such as FAD can exist in oxidized, semiquinone (one-electron reduced), or fully reduced hydroquinone forms, FNR can interact with one and two electron carriers. FNR has a strong preference for NADP(H) vs NAD(H).

                        10        20        30
                ....*....|....*....|....*....|..
gi 40067426  27 IAGGTGITPMLQVIRAIMKDPDDHTVCHLLFA 58
Cdd:cd06197 131 IAGGVGITPFLAMLRAILSSRNTTWDITLLWS 162