{"gene":"PF3D7_1139700","run_date":"2026-09-08T12:51:28","timeline":{"discoveries":[{"year":2008,"finding":"The ferredoxin-NADP(+) reductase (FNR) from Plasmodium falciparum (corresponding to PF3D7_1139700, a glutathione reductase-type/adrenodoxin reductase homolog) was characterized biochemically, with findings indicating novel modes of FAD- and NADP(H)-binding relative to other FNR family members, and adrenodoxin reductase homologs in this family were shown to catalyze the oxidation of NADP(+) to its 4-oxo derivative.","method":"Biochemical characterization and structural comparison (review of recent experimental findings on FNR structure-function relationships)","journal":"Archives of biochemistry and biophysics","confidence":"Low","confidence_rationale":"Tier 3 / Weak — review paper summarizing experimental characterization, single citation of recent findings, no primary in vitro assay or mutagenesis data directly described in the abstract","pmids":["18307973"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1139700 (adrenodoxin reductase, putative) is a glutathione reductase-type ferredoxin-NADP(+) reductase in P. falciparum that catalyzes electron transfer between NADP(H) and ferredoxin/adrenodoxin, exhibits novel FAD- and NADP(H)-binding properties, and its homologs can oxidize NADP(+) to a 4-oxo derivative; it has been proposed as a drug target, but detailed mechanistic or structural characterization in this specific parasite protein remains limited."},"narrative":{"mechanistic_narrative":"PF3D7_1139700 is annotated as a putative adrenodoxin reductase and characterized as a ferredoxin-NADP(+) reductase (FNR) of the glutathione reductase structural type in Plasmodium falciparum, with biochemical evidence indicating novel modes of FAD- and NADP(H)-binding relative to other FNR family members [PMID:18307973]. Within this family, adrenodoxin reductase homologs can catalyze oxidation of NADP(+) to its 4-oxo derivative [PMID:18307973]. Beyond this single biochemical characterization [PMID:18307973], no further mechanistic, structural, or in vivo functional detail specific to PF3D7_1139700 has been characterized in the available corpus.","teleology":[{"year":2008,"claim":"Establishing whether the Plasmodium falciparum FNR/adrenodoxin reductase homolog behaves like canonical FNR enzymes addressed whether this parasite protein could be a distinct, potentially druggable flavoenzyme.","evidence":"Biochemical characterization and structural comparison of P. falciparum FNR within the FNR family","pmids":["18307973"],"confidence":"Low","gaps":["No primary in vitro kinetic assay or mutagenesis data on PF3D7_1139700 itself is described","No structural model of the parasite protein is provided","Physiological electron partner (ferredoxin vs adrenodoxin) and cellular role in P. falciparum are not established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"It remains unknown what the endogenous redox partners, subcellular localization, and biological pathway of PF3D7_1139700 are, and whether it is essential or validated as a drug target in P. falciparum.","evidence":"","pmids":[],"confidence":"Low","gaps":["No genetic knockout or essentiality data","No reconstitution of electron transfer with a defined parasite ferredoxin/adrenodoxin","No structural determination of the parasite enzyme"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["FERREDOXIN/ADRENODOXIN (FAMILY-LEVEL ELECTRON PARTNER; NOT SPECIFICALLY VALIDATED FOR PF3D7_1139700) [#0]"],"other_free_text":["Characterized as a glutathione reductase-type FNR with novel FAD- and NADP(H)-binding modes [#0]","Family homologs oxidize NADP(+) to a 4-oxo derivative [#0]","Proposed as a drug target but without direct target-validation data in the corpus [#0]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"18307973","id":"PMC_18307973","title":"Structural and functional diversity of ferredoxin-NADP(+) reductases.","date":"2008","source":"Archives of biochemistry and biophysics","url":"https://pubmed.ncbi.nlm.nih.gov/18307973","citation_count":127,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["adrenodoxin reductase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"42352277","id":"PMC_42352277","title":"Free Radical Formation in the Reactions of Redox-Active Drugs and Xenobiotics with Mitochondrial Flavoenzymes.","date":"2026","source":"Biomolecules","url":"https://pubmed.ncbi.nlm.nih.gov/42352277","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["adrenodoxin reductase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7440,"output_tokens":558,"usd":0.024473,"retried_sync":true},"stage2":{"model":"claude-opus-4-8","input_tokens":4932,"output_tokens":1152,"usd":0.02673,"stage2_stop_reason":"end_turn"},"total_usd":0.051203,"stage1_batch_id":"msgbatch_01DisAaTypwmC8QwdMBuePHo","stage2_batch_id":"msgbatch_0184zxZTqxiEfdYYfPMfkqjb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2008,\n      \"finding\": \"The ferredoxin-NADP(+) reductase (FNR) from Plasmodium falciparum (corresponding to PF3D7_1139700, a glutathione reductase-type/adrenodoxin reductase homolog) was characterized biochemically, with findings indicating novel modes of FAD- and NADP(H)-binding relative to other FNR family members, and adrenodoxin reductase homologs in this family were shown to catalyze the oxidation of NADP(+) to its 4-oxo derivative.\",\n      \"method\": \"Biochemical characterization and structural comparison (review of recent experimental findings on FNR structure-function relationships)\",\n      \"journal\": \"Archives of biochemistry and biophysics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — review paper summarizing experimental characterization, single citation of recent findings, no primary in vitro assay or mutagenesis data directly described in the abstract\",\n      \"pmids\": [\"18307973\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_1139700 (adrenodoxin reductase, putative) is a glutathione reductase-type ferredoxin-NADP(+) reductase in P. falciparum that catalyzes electron transfer between NADP(H) and ferredoxin/adrenodoxin, exhibits novel FAD- and NADP(H)-binding properties, and its homologs can oxidize NADP(+) to a 4-oxo derivative; it has been proposed as a drug target, but detailed mechanistic or structural characterization in this specific parasite protein remains limited.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1139700 is annotated as a putative adrenodoxin reductase and characterized as a ferredoxin-NADP(+) reductase (FNR) of the glutathione reductase structural type in Plasmodium falciparum, with biochemical evidence indicating novel modes of FAD- and NADP(H)-binding relative to other FNR family members [#0]. Within this family, adrenodoxin reductase homologs can catalyze oxidation of NADP(+) to its 4-oxo derivative [#0]. Beyond this single biochemical characterization [#0], no further mechanistic, structural, or in vivo functional detail specific to PF3D7_1139700 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2008,\n      \"claim\": \"Establishing whether the Plasmodium falciparum FNR/adrenodoxin reductase homolog behaves like canonical FNR enzymes addressed whether this parasite protein could be a distinct, potentially druggable flavoenzyme.\",\n      \"evidence\": \"Biochemical characterization and structural comparison of P. falciparum FNR within the FNR family\",\n      \"pmids\": [\"18307973\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No primary in vitro kinetic assay or mutagenesis data on PF3D7_1139700 itself is described\",\n        \"No structural model of the parasite protein is provided\",\n        \"Physiological electron partner (ferredoxin vs adrenodoxin) and cellular role in P. falciparum are not established\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown what the endogenous redox partners, subcellular localization, and biological pathway of PF3D7_1139700 are, and whether it is essential or validated as a drug target in P. falciparum.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No genetic knockout or essentiality data\",\n        \"No reconstitution of electron transfer with a defined parasite ferredoxin/adrenodoxin\",\n        \"No structural determination of the parasite enzyme\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004324\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0071949\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0050660\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [\"ferredoxin/adrenodoxin (family-level electron partner; not specifically validated for PF3D7_1139700) [#0]\"],\n    \"other_free_text\": [\n      \"Characterized as a glutathione reductase-type FNR with novel FAD- and NADP(H)-binding modes [#0]\",\n      \"Family homologs oxidize NADP(+) to a 4-oxo derivative [#0]\",\n      \"Proposed as a drug target but without direct target-validation data in the corpus [#0]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1139700","name":null,"product":"adrenodoxin reductase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0909300","name":null,"product":"adrenodoxin reductase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0937600","name":null,"product":"adrenodoxin reductase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}