Product Description: ferredoxin--NADP reductase
SignalP Peptide: MKIRFVFILSVLISGVCC
# Transmembrane Domains: 0
EC Numbers: 1.18.1.2 (Ferredoxin--NADP(+) reductase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0020011 | apicoplast |
| Function | GO:0071949 | FAD binding |
| Function | GO:0009055 | electron transfer activity |
| Function | GO:0008937 | ferredoxin-NAD(P) reductase activity |
| Function | GO:0004324 | ferredoxin-NADP+ reductase activity |
| Function | GO:0042802 | identical protein binding |
| Function | GO:0005515 | protein binding |
| Process | GO:0055114 | oxidation-reduction process |
| Process | GO:0009410 | response to xenobiotic stimulus |
Expression by stage (LR - Le Roch et al., and MCA - Malaria Cell Atlas):
| Stage | LR class | MCA mean | MCA prop. zeros |
|---|---|---|---|
| Sporozoite | not expressed | N/A | N/A |
| Ring | expressed | 0.06 | 0.97 |
| Trophozoite | expressed | 0.07 | 0.95 |
| Schizont | expressed | 0.01 | 0.99 |
| Gametocyte | expressed | 0.06 | 0.96 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_0623200
Resistome Missense Mutations: L279F
Resistome Compounds with Missense Mutations: Suloctidil
Resistome # Samples with Disruptive Mutations: 1 (1 missense, 1 "interesting" missense)
Zhang Phenotype: Non - Mutable in CDS
MIS: 0.162 | MFS: -2.798 | #Insertions: 0
PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_1122100)
RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_1122100)
Modification: Mutated | RMgm-4880
More info: PhenoPlasm Link
AlphaFill Uniprot ID: C6KT68
"Best" AlphaFill ligand hit: A2P (adenosine-2'-5'-diphosphate, Local RMSD=0.12) with 2OK7 (Global RMSD=1.25)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 1.18.1.2 | ferredoxin-NADP+ reductase | BRENDA SOAP query unsuccessful |
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| P29477 | Nitric oxide synthase, inducible | Mus musculus | OrthoDB | Ngamma-nitro-L-argininehDDAH inhibitor, 1e(S)-2-Amino-5-formimidamidopentanoic acid (7)hDDAH inhibitor, 1d... |
| P29474 | Nitric oxide synthase, endothelial | OrthoDB | quinolinone, 23quinolinone, 24quinolinone, 40quinolinone, 41... | |
| P35228 | Nitric oxide synthase, inducible | Homo sapiens | OrthoDB | quinolinone, 7quinolinone, 8quinolinone, 9quinolinone, 10... |
| P70313 | Nitric oxide synthase, endothelial | Mus musculus | OrthoDB | CHEMBL1946352 |
| Q06518 | Nitric oxide synthase, inducible | Rattus norvegicus | OrthoDB | CHEMBL1956107ONO-1714L-NIO, 12CHEMBL2414836... |
| P29475 | Nitric oxide synthase, brain | Homo sapiens | OrthoDB | quinolinone, 12quinolinone, 15quinolinone, 19quinolinone, 20... |
| Q28969 | Nitric oxide synthase, endothelial | Sus scrofa | OrthoDB | CHEMBL318427CHEMBL101399CHEMBL100659CHEMBL327287 |
| Q9Z0J4 | Nitric oxide synthase, brain | Mus musculus | OrthoDB | US9783500, Compound 4US9783500, Compound 11US9783500, Compound 12US9783500, Compound 14... |
| Q62600 | Nitric oxide synthase, endothelial | Rattus norvegicus | OrthoDB | nNOS inhibitor, 2CHEMBL3262022CHEMBL3819046CHEMBL3819644... |
| P29476 | Nitric oxide synthase, brain | Rattus norvegicus | OrthoDB | Ngamma-nitro-L-arginineCHEMBL227937CHEMBL228077N omega-Nitro-L-Arginine-Containing Dipeptide, 3... |
Protein Length: 371 | Molecular Weight (kDa): 43.779
UniProt ID(s): C6KT68
PDB ID(s): 2OK7, 2OK8, 3JQP, 3JQQ, 3JQR
Isoelectric Point: 9.6
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR001433 | Oxidoreductase FAD/NAD(P)-binding |
| InterPro | IPR001709 | Flavoprotein pyridine nucleotide cytochrome reductase |
| InterPro | IPR017938 | Riboflavin synthase-like beta-barrel |
| InterPro | IPR039261 | Ferredoxin-NADP reductase (FNR), nucleotide-binding domain |
| PFam | PF00175 | Oxidoreductase FAD/NAD(P)-binding |
| Superfamily | SSF52343 | Ferredoxin-NADP reductase (FNR), nucleotide-binding domain |
| Superfamily | SSF63380 | Riboflavin synthase-like beta-barrel |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 5 | 19 | 8 | 26 |
| disruptive | 6 | 23 | 17 | 46 |
| missense | 6 | 23 | 16 | 40 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 10 | 38 | 16 | 27 |
| disruptive | 11 | 63 | 38 | 88 |
| missense | 11 | 52 | 31 | 53 |
PlasmoDB Total SNPs: 86
Non-coding: 66 | Synonymous: 15 | Nonsynonymous: 5 | Stop Codon: 0
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 12368867 | Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13. | Hall N, Pain A, ..., Barrell BG | 10.1038/nature01095 |
| 17251200 | Cloning and characterization of ferredoxin and ferredoxin-NADP+ reductase fromhuman malaria parasite. | Kimata-Ariga Y, Kurisu G, ..., Hase T | 10.1093/jb/mvm046 |
| 19736991 | Plasmodium falciparum ferredoxin-NADP+ reductase His286 plays a dual role inNADP(H) binding and catalysis. | Crobu D, Canevari G, ..., Aliverti A | 10.1021/bi9013209 |
| 22519987 | A single tyrosine hydroxyl group almost entirely controls the NADPH specificityof Plasmodium falciparum ferredoxin-NADP+ reductase. | Baroni S, Pandini V, Vanoni MA, Aliverti A | 10.1021/bi300078p |
| 29688515 | Plasmodium-specific basic amino acid residues important for the interaction withferredoxin on the surface of ferredoxin-NADP+ reductase. | Kimata-Ariga Y, Yuasa S, ..., Hase T | 10.1093/jb/mvy045 |
| 30212465 | Integrative proteomics and bioinformatic prediction enable a high-confidenceapicoplast proteome in malaria parasites. | Boucher MJ, Ghosh S, ..., Yeh E | 10.1371/journal.pbio.2005895 |
| 32370303 | Reactions of Plasmodium falciparum Ferredoxin: NADP(+) Oxidoreductase with Redox Cycling Xenobiotics: A Mechanistic Study | Lesanavicius M, Aliverti A, Sarlauskas J, Cenas N | 10.3390/ijms21093234 |
| 34509083 | Covalent inhibition of P. falciparum ferredoxin-NADP(+) reductase: Exploringalternative strategies for the development of new antimalarial drugs. | de Rosa M, Nonnis S, Aliverti A | 10.1016/j.bbrc.2021.09.008 |