{"gene":"PF3D7_0814900","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":1996,"finding":"FeSOD (PF3D7_0814900) from P. falciparum is an iron-dependent superoxide dismutase: its activity is cyanide-resistant and hydrogen peroxide-sensitive, consistent with Fe-SOD class. The enzyme was purified as a subunit with N-terminal sequence matching the cloned cDNA, and phylogenetic analysis confirmed it is related to typical Fe-SODs from other protozoa and bacteria.","method":"Enzyme purification, N-terminal sequencing, cDNA cloning and sequencing, phylogenetic analysis (DARWIN system), activity assays with inhibitors","journal":"Molecular and biochemical parasitology","confidence":"High","confidence_rationale":"Tier 1 / Strong — direct biochemical characterization with purification, sequencing, and activity assays; first characterization of FeSOD in Plasmodium; replicated by subsequent studies","pmids":["8920001"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2002,"finding":"Recombinant FeSOD (PF3D7_0814900) is a homodimer containing ~1.7 Fe equivalents per dimer and is sensitive to hydrogen peroxide. EPR analysis revealed two distinct high-spin Fe site environments with different symmetries. Site-directed mutagenesis of residue W71 (W71V) altered the relative proportion of the two EPR signals, reduced thermal stability, and only marginally increased resistance to H2O2 inactivation, indicating W71 is not a primary determinant of H2O2 sensitivity.","method":"Recombinant protein expression in SOD-deficient E. coli, purification, electron paramagnetic resonance (EPR) spectroscopy, site-directed mutagenesis (W71V), activity assays, molecular modelling","journal":"Molecular and biochemical parasitology","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro biochemical characterization with EPR and site-directed mutagenesis; multiple orthogonal methods in single study","pmids":["11897129"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2004,"finding":"FeSOD (PF3D7_0814900, referred to as PfSOD1 in this paper) is cytosolic in P. falciparum intraerythrocytic stages, as determined by immunofluorescence studies. Its mRNA levels are up to 35-fold higher than those of the second SOD gene (PfSOD2), and both SOD mRNAs are up-regulated upon oxidative stress.","method":"Immunofluorescence microscopy, Northern blot analysis","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization by immunofluorescence; mRNA regulation by Northern blot; single lab but two orthogonal methods","pmids":["15279958"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2006,"finding":"The crystal structure of the cytosolic FeSOD (PF3D7_0814900) from P. falciparum was solved at 2.5 Å resolution. The enzyme has a two-domain organization, is a dimer confirmed by ultracentrifugation, and the iron centre is coordinated by three histidines, one aspartate, and one solvent molecule. A hydrogen-bonding lattice links the two active centres. Active site residues are conserved with other Fe/Mn-SODs, suggesting a common catalytic mechanism. The dimer interface differs from human MnSOD, providing a basis for parasite-selective inhibitor design.","method":"Recombinant expression in E. coli, X-ray crystallography (molecular replacement, 2.5 Å), analytical ultracentrifugation","journal":"BMC structural biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure with functional validation (catalytic activity confirmed), multiple orthogonal methods including ultracentrifugation","pmids":["17020617"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"finding":"FeSOD (PF3D7_0814900, referred to as PfSod in this paper) forms a complex with PfDegP (a serine protease), PfHsp70, and enolase, as identified by co-immunoprecipitation and surface plasmon resonance in P. falciparum.","method":"Anti-bait co-immunoprecipitation, surface plasmon resonance","journal":"The FEBS journal","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single co-IP and SPR experiment identifying complex membership; no functional follow-up specifically for FeSOD within the complex","pmids":["24494818"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_0814900 (FeSOD) is a cytosolic, homodimeric iron-dependent superoxide dismutase in P. falciparum whose crystal structure (2.5 Å) shows an iron centre coordinated by three histidines, one aspartate, and a solvent molecule; the enzyme is cyanide-resistant and hydrogen peroxide-sensitive, W71 is not the primary determinant of H2O2 sensitivity, and FeSOD participates in a multi-protein complex with PfDegP, PfHsp70, and enolase as part of the parasite's antioxidant defence."},"narrative":{"mechanistic_narrative":"PF3D7_0814900 (FeSOD) is an iron-dependent superoxide dismutase of Plasmodium falciparum that contributes to the intraerythrocytic parasite's antioxidant defence [PMID:8920001]. Biochemically it belongs to the Fe-SOD class: its activity is cyanide-resistant and hydrogen-peroxide-sensitive, and it was purified and cloned as a subunit whose phylogeny groups with typical protozoan and bacterial Fe-SODs [PMID:8920001]. The functional enzyme is a homodimer carrying roughly 1.7 Fe equivalents per dimer, and its 2.5 Å crystal structure shows a two-domain fold with an iron centre coordinated by three histidines, one aspartate, and a solvent molecule, plus a hydrogen-bonding lattice linking the two active centres; the dimer interface diverges from human MnSOD, defining a basis for parasite-selective inhibitor design [PMID:11897129, PMID:17020617]. EPR resolves two distinct high-spin Fe environments, and mutagenesis established that W71 is not a primary determinant of H2O2 sensitivity [PMID:11897129]. FeSOD is cytosolic in intraerythrocytic stages, its mRNA is far more abundant than that of the second parasite SOD gene, and both are up-regulated by oxidative stress [PMID:15279958]. Beyond this enzymatic and structural characterization, the corpus places FeSOD in a multi-protein complex with PfDegP, PfHsp70, and enolase [PMID:24494818]; no functional role for FeSOD within that complex has been characterized in the available corpus.","teleology":[{"year":1996,"claim":"Establishing which SOD class the P. falciparum enzyme belongs to was needed to define the parasite's superoxide-scavenging chemistry; purification and inhibitor profiling identified it as a genuine iron-dependent SOD distinct from Cu/Zn enzymes.","evidence":"enzyme purification, N-terminal sequencing, cDNA cloning, phylogenetic analysis, and activity assays with inhibitors in P. falciparum","pmids":["8920001"],"confidence":"High","gaps":["Does not establish subcellular localization or in vivo contribution to parasite survival","Catalytic mechanism not resolved at residue level"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2002,"claim":"The oligomeric state, metal stoichiometry, and the residue basis of H2O2 sensitivity were unknown; recombinant characterization showed a homodimer with ~1.7 Fe per dimer, two distinct Fe environments, and ruled out W71 as the primary H2O2-sensitivity determinant.","evidence":"recombinant expression in SOD-deficient E. coli, EPR spectroscopy, W71V site-directed mutagenesis, activity assays, and molecular modelling","pmids":["11897129"],"confidence":"High","gaps":["The actual structural determinant of H2O2 sensitivity remains unidentified","Functional meaning of the two distinct Fe EPR environments not resolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2004,"claim":"Whether FeSOD acts in the cytosol and how it is expressed relative to the second parasite SOD was unresolved; localization and expression analysis placed it in the cytosol with predominant and stress-inducible mRNA expression.","evidence":"immunofluorescence microscopy and Northern blot analysis in P. falciparum intraerythrocytic stages","pmids":["15279958"],"confidence":"Medium","gaps":["mRNA abundance does not establish relative protein-level contribution","Does not test whether FeSOD is required for oxidative-stress survival"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2006,"claim":"A high-resolution structural model was needed to define the active site and to enable selective drug design; the crystal structure revealed the iron coordination geometry and a dimer interface distinct from human MnSOD.","evidence":"recombinant expression, X-ray crystallography at 2.5 Å by molecular replacement, and analytical ultracentrifugation in P. falciparum","pmids":["17020617"],"confidence":"High","gaps":["No inhibitor-bound structure or validated selective inhibitor reported","Catalytic cycle not directly captured"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"claim":"Whether FeSOD functions in isolation or within a protein assembly was open; interaction analysis placed FeSOD in a complex with PfDegP, PfHsp70, and enolase.","evidence":"anti-bait co-immunoprecipitation and surface plasmon resonance in P. falciparum","pmids":["24494818"],"confidence":"Low","gaps":["Single co-IP/SPR study without reciprocal validation or knockdown","No functional role for FeSOD within the complex demonstrated","Stoichiometry and physiological trigger of complex formation unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The in vivo requirement of FeSOD for parasite antioxidant defence and survival, and its functional role within the PfDegP/PfHsp70/enolase complex, remain to be established.","evidence":"","pmids":[],"confidence":"Low","gaps":["No genetic knockout/knockdown phenotype in the corpus","No validated selective inhibitor despite structural rationale","Functional consequence of complex membership uncharacterized"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["FeSOD–PfDegP–PfHsp70–enolase complex [#4]"],"partners":["PFDEGP [#4]","PFHSP70 [#4]","ENOLASE [#4]"],"other_free_text":["Fe-SOD class: cyanide-resistant, hydrogen-peroxide-sensitive activity [#0]","Homodimer with ~1.7 Fe equivalents per dimer; two distinct high-spin Fe EPR environments [#1]","W71 is not a primary determinant of H2O2 sensitivity (W71V mutagenesis) [#1]","2.5 Å crystal structure: two-domain fold, iron coordinated by three histidines, one aspartate, one solvent molecule; hydrogen-bonding lattice links two active centres [#3]","Dimer interface differs from human MnSOD, providing basis for parasite-selective inhibitor design [#3]","mRNA up to 35-fold higher than the second parasite SOD gene and up-regulated under oxidative stress [#2]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"8920001","id":"PMC_8920001","title":"Characterization of iron-dependent endogenous superoxide dismutase of Plasmodium falciparum.","date":"1996","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/8920001","citation_count":65,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"15279958","id":"PMC_15279958","title":"Identification of a mitochondrial superoxide dismutase with an unusual targeting sequence in Plasmodium falciparum.","date":"2004","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/15279958","citation_count":43,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"17020617","id":"PMC_17020617","title":"The crystal structure of superoxide dismutase from Plasmodium falciparum.","date":"2006","source":"BMC structural biology","url":"https://pubmed.ncbi.nlm.nih.gov/17020617","citation_count":26,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfFeSOD"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"11897129","id":"PMC_11897129","title":"Biochemical and electron paramagnetic resonance study of the iron superoxide dismutase from Plasmodium falciparum.","date":"2002","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/11897129","citation_count":25,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["FeSOD","superoxide dismutase [Fe]"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"24494818","id":"PMC_24494818","title":"A secretory multifunctional serine protease, DegP of Plasmodium falciparum, plays an important role in thermo-oxidative stress, parasite growth and development.","date":"2014","source":"The FEBS journal","url":"https://pubmed.ncbi.nlm.nih.gov/24494818","citation_count":16,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25091832","id":"PMC_25091832","title":"Molecular cloning and biochemical characterization of iron superoxide dismutase from the rodent malaria parasite Plasmodium vinckei.","date":"2014","source":"Parasitology international","url":"https://pubmed.ncbi.nlm.nih.gov/25091832","citation_count":11,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"10599926","id":"PMC_10599926","title":"Cloning and characterization of iron-containing superoxide dismutase from the human malaria species Plasmodium ovale, P. malariae and P. vivax.","date":"1999","source":"Parasitology research","url":"https://pubmed.ncbi.nlm.nih.gov/10599926","citation_count":9,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["FeSOD"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"10585544","id":"PMC_10585544","title":"Analysis of genetic diversity at the iron-containing superoxide dismutase locus in Plasmodium falciparum wild isolates.","date":"1999","source":"FEMS microbiology letters","url":"https://pubmed.ncbi.nlm.nih.gov/10585544","citation_count":3,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["FeSOD"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6510,"output_tokens":1596,"usd":0.021735,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6648,"output_tokens":2803,"usd":0.051658,"stage2_stop_reason":"end_turn"},"total_usd":0.073393,"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\": 1996,\n      \"finding\": \"FeSOD (PF3D7_0814900) from P. falciparum is an iron-dependent superoxide dismutase: its activity is cyanide-resistant and hydrogen peroxide-sensitive, consistent with Fe-SOD class. The enzyme was purified as a subunit with N-terminal sequence matching the cloned cDNA, and phylogenetic analysis confirmed it is related to typical Fe-SODs from other protozoa and bacteria.\",\n      \"method\": \"Enzyme purification, N-terminal sequencing, cDNA cloning and sequencing, phylogenetic analysis (DARWIN system), activity assays with inhibitors\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — direct biochemical characterization with purification, sequencing, and activity assays; first characterization of FeSOD in Plasmodium; replicated by subsequent studies\",\n      \"pmids\": [\"8920001\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"Recombinant FeSOD (PF3D7_0814900) is a homodimer containing ~1.7 Fe equivalents per dimer and is sensitive to hydrogen peroxide. EPR analysis revealed two distinct high-spin Fe site environments with different symmetries. Site-directed mutagenesis of residue W71 (W71V) altered the relative proportion of the two EPR signals, reduced thermal stability, and only marginally increased resistance to H2O2 inactivation, indicating W71 is not a primary determinant of H2O2 sensitivity.\",\n      \"method\": \"Recombinant protein expression in SOD-deficient E. coli, purification, electron paramagnetic resonance (EPR) spectroscopy, site-directed mutagenesis (W71V), activity assays, molecular modelling\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro biochemical characterization with EPR and site-directed mutagenesis; multiple orthogonal methods in single study\",\n      \"pmids\": [\"11897129\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"FeSOD (PF3D7_0814900, referred to as PfSOD1 in this paper) is cytosolic in P. falciparum intraerythrocytic stages, as determined by immunofluorescence studies. Its mRNA levels are up to 35-fold higher than those of the second SOD gene (PfSOD2), and both SOD mRNAs are up-regulated upon oxidative stress.\",\n      \"method\": \"Immunofluorescence microscopy, Northern blot analysis\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization by immunofluorescence; mRNA regulation by Northern blot; single lab but two orthogonal methods\",\n      \"pmids\": [\"15279958\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"The crystal structure of the cytosolic FeSOD (PF3D7_0814900) from P. falciparum was solved at 2.5 Å resolution. The enzyme has a two-domain organization, is a dimer confirmed by ultracentrifugation, and the iron centre is coordinated by three histidines, one aspartate, and one solvent molecule. A hydrogen-bonding lattice links the two active centres. Active site residues are conserved with other Fe/Mn-SODs, suggesting a common catalytic mechanism. The dimer interface differs from human MnSOD, providing a basis for parasite-selective inhibitor design.\",\n      \"method\": \"Recombinant expression in E. coli, X-ray crystallography (molecular replacement, 2.5 Å), analytical ultracentrifugation\",\n      \"journal\": \"BMC structural biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure with functional validation (catalytic activity confirmed), multiple orthogonal methods including ultracentrifugation\",\n      \"pmids\": [\"17020617\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"FeSOD (PF3D7_0814900, referred to as PfSod in this paper) forms a complex with PfDegP (a serine protease), PfHsp70, and enolase, as identified by co-immunoprecipitation and surface plasmon resonance in P. falciparum.\",\n      \"method\": \"Anti-bait co-immunoprecipitation, surface plasmon resonance\",\n      \"journal\": \"The FEBS journal\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single co-IP and SPR experiment identifying complex membership; no functional follow-up specifically for FeSOD within the complex\",\n      \"pmids\": [\"24494818\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_0814900 (FeSOD) is a cytosolic, homodimeric iron-dependent superoxide dismutase in P. falciparum whose crystal structure (2.5 Å) shows an iron centre coordinated by three histidines, one aspartate, and a solvent molecule; the enzyme is cyanide-resistant and hydrogen peroxide-sensitive, W71 is not the primary determinant of H2O2 sensitivity, and FeSOD participates in a multi-protein complex with PfDegP, PfHsp70, and enolase as part of the parasite's antioxidant defence.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0814900 (FeSOD) is an iron-dependent superoxide dismutase of Plasmodium falciparum that contributes to the intraerythrocytic parasite's antioxidant defence [#0]. Biochemically it belongs to the Fe-SOD class: its activity is cyanide-resistant and hydrogen-peroxide-sensitive, and it was purified and cloned as a subunit whose phylogeny groups with typical protozoan and bacterial Fe-SODs [#0]. The functional enzyme is a homodimer carrying roughly 1.7 Fe equivalents per dimer, and its 2.5 Å crystal structure shows a two-domain fold with an iron centre coordinated by three histidines, one aspartate, and a solvent molecule, plus a hydrogen-bonding lattice linking the two active centres; the dimer interface diverges from human MnSOD, defining a basis for parasite-selective inhibitor design [#1, #3]. EPR resolves two distinct high-spin Fe environments, and mutagenesis established that W71 is not a primary determinant of H2O2 sensitivity [#1]. FeSOD is cytosolic in intraerythrocytic stages, its mRNA is far more abundant than that of the second parasite SOD gene, and both are up-regulated by oxidative stress [#2]. Beyond this enzymatic and structural characterization, the corpus places FeSOD in a multi-protein complex with PfDegP, PfHsp70, and enolase [#4]; no functional role for FeSOD within that complex has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 1996,\n      \"claim\": \"Establishing which SOD class the P. falciparum enzyme belongs to was needed to define the parasite's superoxide-scavenging chemistry; purification and inhibitor profiling identified it as a genuine iron-dependent SOD distinct from Cu/Zn enzymes.\",\n      \"evidence\": \"enzyme purification, N-terminal sequencing, cDNA cloning, phylogenetic analysis, and activity assays with inhibitors in P. falciparum\",\n      \"pmids\": [\"8920001\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Does not establish subcellular localization or in vivo contribution to parasite survival\", \"Catalytic mechanism not resolved at residue level\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"The oligomeric state, metal stoichiometry, and the residue basis of H2O2 sensitivity were unknown; recombinant characterization showed a homodimer with ~1.7 Fe per dimer, two distinct Fe environments, and ruled out W71 as the primary H2O2-sensitivity determinant.\",\n      \"evidence\": \"recombinant expression in SOD-deficient E. coli, EPR spectroscopy, W71V site-directed mutagenesis, activity assays, and molecular modelling\",\n      \"pmids\": [\"11897129\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"The actual structural determinant of H2O2 sensitivity remains unidentified\", \"Functional meaning of the two distinct Fe EPR environments not resolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Whether FeSOD acts in the cytosol and how it is expressed relative to the second parasite SOD was unresolved; localization and expression analysis placed it in the cytosol with predominant and stress-inducible mRNA expression.\",\n      \"evidence\": \"immunofluorescence microscopy and Northern blot analysis in P. falciparum intraerythrocytic stages\",\n      \"pmids\": [\"15279958\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"mRNA abundance does not establish relative protein-level contribution\", \"Does not test whether FeSOD is required for oxidative-stress survival\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"A high-resolution structural model was needed to define the active site and to enable selective drug design; the crystal structure revealed the iron coordination geometry and a dimer interface distinct from human MnSOD.\",\n      \"evidence\": \"recombinant expression, X-ray crystallography at 2.5 Å by molecular replacement, and analytical ultracentrifugation in P. falciparum\",\n      \"pmids\": [\"17020617\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No inhibitor-bound structure or validated selective inhibitor reported\", \"Catalytic cycle not directly captured\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Whether FeSOD functions in isolation or within a protein assembly was open; interaction analysis placed FeSOD in a complex with PfDegP, PfHsp70, and enolase.\",\n      \"evidence\": \"anti-bait co-immunoprecipitation and surface plasmon resonance in P. falciparum\",\n      \"pmids\": [\"24494818\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single co-IP/SPR study without reciprocal validation or knockdown\", \"No functional role for FeSOD within the complex demonstrated\", \"Stoichiometry and physiological trigger of complex formation unknown\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The in vivo requirement of FeSOD for parasite antioxidant defence and survival, and its functional role within the PfDegP/PfHsp70/enolase complex, remain to be established.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No genetic knockout/knockdown phenotype in the corpus\", \"No validated selective inhibitor despite structural rationale\", \"Functional consequence of complex membership uncharacterized\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004784\", \"supporting_discovery_ids\": [0, 1, 3]},\n      {\"term_id\": \"GO:0005506\", \"supporting_discovery_ids\": [1, 3]},\n      {\"term_id\": \"GO:0042803\", \"supporting_discovery_ids\": [1, 3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0019430\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"GO:0006979\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [\n      \"FeSOD–PfDegP–PfHsp70–enolase complex [#4]\"\n    ],\n    \"partners\": [\n      \"PfDegP [#4]\",\n      \"PfHsp70 [#4]\",\n      \"enolase [#4]\"\n    ],\n    \"other_free_text\": [\n      \"Fe-SOD class: cyanide-resistant, hydrogen-peroxide-sensitive activity [#0]\",\n      \"Homodimer with ~1.7 Fe equivalents per dimer; two distinct high-spin Fe EPR environments [#1]\",\n      \"W71 is not a primary determinant of H2O2 sensitivity (W71V mutagenesis) [#1]\",\n      \"2.5 Å crystal structure: two-domain fold, iron coordinated by three histidines, one aspartate, one solvent molecule; hydrogen-bonding lattice links two active centres [#3]\",\n      \"Dimer interface differs from human MnSOD, providing basis for parasite-selective inhibitor design [#3]\",\n      \"mRNA up to 35-fold higher than the second parasite SOD gene and up-regulated under oxidative stress [#2]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0814900","name":null,"product":"superoxide dismutase [Fe]","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1422700","name":null,"product":"superoxide dismutase [Fe], putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1425400","name":null,"product":"superoxide dismutase [Fe], putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"FeSOD","evaluation":null}