{"gene":"PF3D7_0608800","run_date":"2026-09-07T10:55:52","timeline":{"discoveries":[{"year":1993,"finding":"A putative ornithine aminotransferase gene of P. falciparum (PF3D7_0608800) was identified and characterized at the molecular level.","method":"Gene characterization (cloning/sequencing)","journal":"Molecular and biochemical parasitology","confidence":"Low","confidence_rationale":"Tier 4 / Weak — abstract not available; minimal methodological detail recoverable","pmids":["8264733"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2001,"finding":"P. falciparum OAT (PF3D7_0608800) was cloned, expressed, and shown to catalyze the reversible transamination of ornithine or N-acetylornithine with alpha-ketoglutarate, and of glutamate-5-semialdehyde with glutamate and alanine; the enzyme displays narrow substrate specificity. The ornithine analogue canaline inhibits OAT uncompetitively with a Ki of 492 ± 98 nM. Radiolabeling experiments showed that P. falciparum converts only 0.68% of exogenous glutamine to ornithine over 3.5 h, indicating the OAT-mediated biosynthetic route from glutamine to ornithine is of limited quantitative importance.","method":"Heterologous expression, in vitro enzymatic assay, substrate specificity profiling, inhibitor kinetics, radiolabeled precursor incorporation","journal":"Molecular and biochemical parasitology","confidence":"High","confidence_rationale":"Tier 1 / Strong — direct in vitro biochemical reconstitution with kinetic characterization and multiple orthogonal methods (expression, enzyme assay, inhibitor Ki, isotope labeling)","pmids":["11704268"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":"3D7"}]},{"year":2009,"finding":"P. falciparum OAT (PF3D7_0608800) physically interacts with thioredoxin (Trx), glutaredoxin (Grx), and plasmoredoxin (Plrx); binding of Trx and Grx to OAT was verified by BIAcore surface plasmon resonance, and Trx was shown to enhance OAT enzymatic activity in vitro.","method":"Active-site mutant affinity trapping of target proteins from P. falciparum cell extracts, mass spectrometry identification, BIAcore surface plasmon resonance binding verification, in vitro enzymatic activity assay","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — interaction confirmed by SPR (orthogonal to affinity trapping), functional consequence (activity enhancement) measured in enzymatic assay, multiple redoxins tested","pmids":["19360125"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"finding":"The crystal structure of P. falciparum OAT (PF3D7_0608800) was solved at 2.3 Å resolution, revealing that the substrate-binding loop contains two cysteines (Cys154 and Cys163) absent in human OAT. Site-directed mutagenesis showed that Cys154 and Cys163 mediate interaction with Trx; additionally, the Cys154→Ser mutant has strongly reduced enzymatic activity, consistent with a role for Cys154 in ornithine binding. Trx activates P. falciparum OAT ~10-fold, an effect not observed for the human enzyme, and these cysteines are conserved across Plasmodium species but absent in other organisms.","method":"X-ray crystallography (2.3 Å), site-directed mutagenesis (Cys154Ser, Cys163 mutants), in vitro enzymatic activity assays, comparative structural analysis with human OAT","journal":"Journal of molecular biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure combined with site-directed mutagenesis and functional enzyme assays in a single rigorous study, multiple orthogonal methods","pmids":["20673832"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"finding":"Loss-of-function mutations in PfApiAT2 (not in arginase or OAT/PF3D7_0608800) are the primary genetic driver of the adaptive proline response (APR) in P. falciparum resistance to prolyl-tRNA synthetase inhibitors; alterations in OAT were explicitly ruled out as mediators of the APR.","method":"Genetic mapping of resistance mutations, reversion of PfApiAT2 mutations to wild type, metabolomics (intracellular proline measurement)","journal":"Cell chemical biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — negative result for OAT established by genetic reversion and metabolomics in a single study; finding is mechanistically informative (OAT not involved in APR)","pmids":["41061700"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"P. falciparum OAT (PF3D7_0608800) is a pyridoxal-phosphate-dependent enzyme that catalyzes the reversible transamination of ornithine (or N-acetylornithine) with alpha-ketoglutarate to produce glutamate-5-semialdehyde and glutamate, thereby participating in ornithine homeostasis, proline biosynthesis, and polyamine metabolism; its activity is uniquely enhanced ~10-fold by thioredoxin through a redox interaction mediated by two Plasmodium-specific active-site cysteines (Cys154 and Cys163) identified in the 2.3 Å crystal structure, with Cys154 also required for optimal ornithine binding, while the enzyme is competitively inhibitable by canaline (Ki ~492 nM) and is not involved in the adaptive proline response to prolyl-tRNA synthetase inhibitors."},"narrative":{"mechanistic_narrative":"PF3D7_0608800 (OAT) is a pyridoxal-phosphate-dependent aminotransferase of Plasmodium falciparum that catalyzes the reversible transamination of ornithine or N-acetylornithine with alpha-ketoglutarate, and of glutamate-5-semialdehyde with glutamate and alanine, placing it within ornithine and glutamate interconversion [PMID:11704268]. The enzyme shows narrow substrate specificity and is inhibited by the ornithine analogue canaline (Ki ~492 nM); isotope-tracing shows that the OAT-mediated biosynthetic route from glutamine to ornithine is quantitatively minor in the parasite [PMID:11704268]. A distinctive feature of the P. falciparum enzyme is a redox-regulated activation: OAT physically interacts with thioredoxin, glutaredoxin, and plasmoredoxin, and thioredoxin enhances its activity in vitro [PMID:19360125]. The 2.3 Å crystal structure identifies two active-site-loop cysteines, Cys154 and Cys163, absent from human OAT and conserved across Plasmodium, that mediate the thioredoxin interaction and drive an ~10-fold activation not seen for the human enzyme; Cys154 is additionally required for optimal enzymatic activity, consistent with a role in ornithine binding [PMID:20673832]. OAT is not the genetic driver of the adaptive proline response underlying resistance to prolyl-tRNA synthetase inhibitors [PMID:41061700]. Beyond these findings, the in vivo metabolic role and essentiality of PF3D7_0608800 have not been characterized in the available corpus.","teleology":[{"year":1993,"claim":"Establishing that P. falciparum encodes a candidate ornithine aminotransferase provided the molecular starting point for characterizing amino-acid metabolism in the parasite.","evidence":"Molecular cloning and sequencing of a putative OAT gene","pmids":["8264733"],"confidence":"Low","gaps":["Abstract unavailable; enzymatic activity not demonstrated at this stage","No functional or localization data"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2001,"claim":"Whether the gene product was catalytically active and metabolically important was resolved by reconstituting the enzyme and measuring its reactions, inhibition, and flux contribution.","evidence":"Heterologous expression, in vitro transamination assays, substrate profiling, canaline inhibitor kinetics, and radiolabeled precursor incorporation in P. falciparum 3D7","pmids":["11704268"],"confidence":"High","gaps":["Physiological direction of the reaction in vivo not established","Consequence of the low glutamine-to-ornithine flux for parasite metabolism unresolved","No genetic knockout of the gene"],"attribution":[{"species":"Plasmodium falciparum","strain":"3D7"}]},{"year":2009,"claim":"The question of how OAT activity is regulated was addressed by identifying redoxin partners and showing thioredoxin functionally activates the enzyme.","evidence":"Active-site mutant affinity trapping with MS identification, BIAcore SPR binding verification for Trx and Grx, and in vitro activity assay","pmids":["19360125"],"confidence":"High","gaps":["Structural basis of the Trx interaction not defined at this stage","Physiological significance of redox regulation in vivo not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"claim":"The structural and molecular basis of Plasmodium-specific redox activation was resolved, revealing parasite-unique active-site cysteines that could be targeted for selective inhibition.","evidence":"2.3 Å X-ray crystallography, site-directed mutagenesis of Cys154 and Cys163, enzyme assays, and comparative analysis with human OAT","pmids":["20673832"],"confidence":"High","gaps":["Redox activation demonstrated in vitro but not in living parasites","Whether the ~10-fold activation modulates flux under physiological conditions unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"claim":"Whether OAT mediates parasite adaptation to prolyl-tRNA synthetase inhibitors was tested and excluded, refining the pathway responsible for the adaptive proline response.","evidence":"Genetic mapping of resistance mutations, reversion of PfApiAT2 to wild type, and metabolomic proline measurement in P. falciparum","pmids":["41061700"],"confidence":"Medium","gaps":["Negative result establishing non-involvement rather than a positive OAT function","Does not address OAT's role in other metabolic contexts"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The in vivo metabolic role, essentiality, and druggability of PF3D7_0608800 in the parasite life cycle remain to be defined.","evidence":"No genetic loss-of-function characterization of OAT itself present in the corpus","pmids":[],"confidence":"Low","gaps":["No knockout/conditional knockdown of OAT reported","Subcellular localization not established","Physiological relevance of redox activation in vivo untested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["THIOREDOXIN (TRX) — DIRECT INTERACTOR, ACTIVATES OAT ~10-FOLD VIA CYS154/CYS163 [#2, #3]","GLUTAREDOXIN (GRX) — BINDING VERIFIED BY SPR [#2]","PLASMOREDOXIN (PLRX) — INTERACTOR IDENTIFIED BY AFFINITY TRAPPING [#2]"],"other_free_text":["Inhibited by the ornithine analogue canaline (Ki ~492 nM) [#1]","Plasmodium-specific active-site cysteines Cys154 and Cys163 mediate thioredoxin-dependent redox activation; Cys154 also required for ornithine binding/activity [#3]","OAT-mediated glutamine-to-ornithine flux is quantitatively minor in P. falciparum [#1]","OAT is explicitly not the genetic driver of the adaptive proline response to prolyl-tRNA synthetase inhibitors [#4]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"19360125","id":"PMC_19360125","title":"Identification of proteins targeted by the thioredoxin superfamily in Plasmodium falciparum.","date":"2009","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/19360125","citation_count":69,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["OAT","ornithine aminotransferase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"11704268","id":"PMC_11704268","title":"Characterization of the ornithine aminotransferase from Plasmodium falciparum.","date":"2001","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/11704268","citation_count":32,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ornithine aminotransferase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"20673832","id":"PMC_20673832","title":"Redox regulation of Plasmodium falciparum ornithine δ-aminotransferase.","date":"2010","source":"Journal of molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/20673832","citation_count":31,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["OAT"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"8264733","id":"PMC_8264733","title":"Characterization of a putative ornithine aminotransferase gene of Plasmodium falciparum.","date":"1993","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/8264733","citation_count":5,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ornithine aminotransferase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41061700","id":"PMC_41061700","title":"Disruption of P. falciparum amino acid transporter elevates intracellular proline and induces resistance to Prolyl-tRNA synthetase inhibitors.","date":"2025","source":"Cell chemical biology","url":"https://pubmed.ncbi.nlm.nih.gov/41061700","citation_count":4,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ornithine aminotransferase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5104,"output_tokens":1731,"usd":0.020639,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6797,"output_tokens":2614,"usd":0.049668,"stage2_stop_reason":"end_turn"},"total_usd":0.070307,"stage1_batch_id":"msgbatch_01DbiymDmubkPpYvdbAu5a7V","stage2_batch_id":"msgbatch_012TbrWvMRH129T7PQ4SmvrJ","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1993,\n      \"finding\": \"A putative ornithine aminotransferase gene of P. falciparum (PF3D7_0608800) was identified and characterized at the molecular level.\",\n      \"method\": \"Gene characterization (cloning/sequencing)\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — abstract not available; minimal methodological detail recoverable\",\n      \"pmids\": [\"8264733\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"P. falciparum OAT (PF3D7_0608800) was cloned, expressed, and shown to catalyze the reversible transamination of ornithine or N-acetylornithine with alpha-ketoglutarate, and of glutamate-5-semialdehyde with glutamate and alanine; the enzyme displays narrow substrate specificity. The ornithine analogue canaline inhibits OAT uncompetitively with a Ki of 492 ± 98 nM. Radiolabeling experiments showed that P. falciparum converts only 0.68% of exogenous glutamine to ornithine over 3.5 h, indicating the OAT-mediated biosynthetic route from glutamine to ornithine is of limited quantitative importance.\",\n      \"method\": \"Heterologous expression, in vitro enzymatic assay, substrate specificity profiling, inhibitor kinetics, radiolabeled precursor incorporation\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — direct in vitro biochemical reconstitution with kinetic characterization and multiple orthogonal methods (expression, enzyme assay, inhibitor Ki, isotope labeling)\",\n      \"pmids\": [\"11704268\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"3D7\"}]\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"P. falciparum OAT (PF3D7_0608800) physically interacts with thioredoxin (Trx), glutaredoxin (Grx), and plasmoredoxin (Plrx); binding of Trx and Grx to OAT was verified by BIAcore surface plasmon resonance, and Trx was shown to enhance OAT enzymatic activity in vitro.\",\n      \"method\": \"Active-site mutant affinity trapping of target proteins from P. falciparum cell extracts, mass spectrometry identification, BIAcore surface plasmon resonance binding verification, in vitro enzymatic activity assay\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — interaction confirmed by SPR (orthogonal to affinity trapping), functional consequence (activity enhancement) measured in enzymatic assay, multiple redoxins tested\",\n      \"pmids\": [\"19360125\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"The crystal structure of P. falciparum OAT (PF3D7_0608800) was solved at 2.3 Å resolution, revealing that the substrate-binding loop contains two cysteines (Cys154 and Cys163) absent in human OAT. Site-directed mutagenesis showed that Cys154 and Cys163 mediate interaction with Trx; additionally, the Cys154→Ser mutant has strongly reduced enzymatic activity, consistent with a role for Cys154 in ornithine binding. Trx activates P. falciparum OAT ~10-fold, an effect not observed for the human enzyme, and these cysteines are conserved across Plasmodium species but absent in other organisms.\",\n      \"method\": \"X-ray crystallography (2.3 Å), site-directed mutagenesis (Cys154Ser, Cys163 mutants), in vitro enzymatic activity assays, comparative structural analysis with human OAT\",\n      \"journal\": \"Journal of molecular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure combined with site-directed mutagenesis and functional enzyme assays in a single rigorous study, multiple orthogonal methods\",\n      \"pmids\": [\"20673832\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Loss-of-function mutations in PfApiAT2 (not in arginase or OAT/PF3D7_0608800) are the primary genetic driver of the adaptive proline response (APR) in P. falciparum resistance to prolyl-tRNA synthetase inhibitors; alterations in OAT were explicitly ruled out as mediators of the APR.\",\n      \"method\": \"Genetic mapping of resistance mutations, reversion of PfApiAT2 mutations to wild type, metabolomics (intracellular proline measurement)\",\n      \"journal\": \"Cell chemical biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — negative result for OAT established by genetic reversion and metabolomics in a single study; finding is mechanistically informative (OAT not involved in APR)\",\n      \"pmids\": [\"41061700\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"P. falciparum OAT (PF3D7_0608800) is a pyridoxal-phosphate-dependent enzyme that catalyzes the reversible transamination of ornithine (or N-acetylornithine) with alpha-ketoglutarate to produce glutamate-5-semialdehyde and glutamate, thereby participating in ornithine homeostasis, proline biosynthesis, and polyamine metabolism; its activity is uniquely enhanced ~10-fold by thioredoxin through a redox interaction mediated by two Plasmodium-specific active-site cysteines (Cys154 and Cys163) identified in the 2.3 Å crystal structure, with Cys154 also required for optimal ornithine binding, while the enzyme is competitively inhibitable by canaline (Ki ~492 nM) and is not involved in the adaptive proline response to prolyl-tRNA synthetase inhibitors.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0608800 (OAT) is a pyridoxal-phosphate-dependent aminotransferase of Plasmodium falciparum that catalyzes the reversible transamination of ornithine or N-acetylornithine with alpha-ketoglutarate, and of glutamate-5-semialdehyde with glutamate and alanine, placing it within ornithine and glutamate interconversion [#1]. The enzyme shows narrow substrate specificity and is inhibited by the ornithine analogue canaline (Ki ~492 nM); isotope-tracing shows that the OAT-mediated biosynthetic route from glutamine to ornithine is quantitatively minor in the parasite [#1]. A distinctive feature of the P. falciparum enzyme is a redox-regulated activation: OAT physically interacts with thioredoxin, glutaredoxin, and plasmoredoxin, and thioredoxin enhances its activity in vitro [#2]. The 2.3 Å crystal structure identifies two active-site-loop cysteines, Cys154 and Cys163, absent from human OAT and conserved across Plasmodium, that mediate the thioredoxin interaction and drive an ~10-fold activation not seen for the human enzyme; Cys154 is additionally required for optimal enzymatic activity, consistent with a role in ornithine binding [#3]. OAT is not the genetic driver of the adaptive proline response underlying resistance to prolyl-tRNA synthetase inhibitors [#4]. Beyond these findings, the in vivo metabolic role and essentiality of PF3D7_0608800 have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 1993,\n      \"claim\": \"Establishing that P. falciparum encodes a candidate ornithine aminotransferase provided the molecular starting point for characterizing amino-acid metabolism in the parasite.\",\n      \"evidence\": \"Molecular cloning and sequencing of a putative OAT gene\",\n      \"pmids\": [\"8264733\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Abstract unavailable; enzymatic activity not demonstrated at this stage\", \"No functional or localization data\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2001,\n      \"claim\": \"Whether the gene product was catalytically active and metabolically important was resolved by reconstituting the enzyme and measuring its reactions, inhibition, and flux contribution.\",\n      \"evidence\": \"Heterologous expression, in vitro transamination assays, substrate profiling, canaline inhibitor kinetics, and radiolabeled precursor incorporation in P. falciparum 3D7\",\n      \"pmids\": [\"11704268\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Physiological direction of the reaction in vivo not established\", \"Consequence of the low glutamine-to-ornithine flux for parasite metabolism unresolved\", \"No genetic knockout of the gene\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"3D7\"}]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"The question of how OAT activity is regulated was addressed by identifying redoxin partners and showing thioredoxin functionally activates the enzyme.\",\n      \"evidence\": \"Active-site mutant affinity trapping with MS identification, BIAcore SPR binding verification for Trx and Grx, and in vitro activity assay\",\n      \"pmids\": [\"19360125\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of the Trx interaction not defined at this stage\", \"Physiological significance of redox regulation in vivo not tested\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"The structural and molecular basis of Plasmodium-specific redox activation was resolved, revealing parasite-unique active-site cysteines that could be targeted for selective inhibition.\",\n      \"evidence\": \"2.3 Å X-ray crystallography, site-directed mutagenesis of Cys154 and Cys163, enzyme assays, and comparative analysis with human OAT\",\n      \"pmids\": [\"20673832\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Redox activation demonstrated in vitro but not in living parasites\", \"Whether the ~10-fold activation modulates flux under physiological conditions unknown\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Whether OAT mediates parasite adaptation to prolyl-tRNA synthetase inhibitors was tested and excluded, refining the pathway responsible for the adaptive proline response.\",\n      \"evidence\": \"Genetic mapping of resistance mutations, reversion of PfApiAT2 to wild type, and metabolomic proline measurement in P. falciparum\",\n      \"pmids\": [\"41061700\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Negative result establishing non-involvement rather than a positive OAT function\", \"Does not address OAT's role in other metabolic contexts\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The in vivo metabolic role, essentiality, and druggability of PF3D7_0608800 in the parasite life cycle remain to be defined.\",\n      \"evidence\": \"No genetic loss-of-function characterization of OAT itself present in the corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No knockout/conditional knockdown of OAT reported\", \"Subcellular localization not established\", \"Physiological relevance of redox activation in vivo untested\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004587\", \"supporting_discovery_ids\": [1, 3]},\n      {\"term_id\": \"GO:0030170\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"GO:0008483\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006591\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0006560\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"Thioredoxin (Trx) — direct interactor, activates OAT ~10-fold via Cys154/Cys163 [#2, #3]\",\n      \"Glutaredoxin (Grx) — binding verified by SPR [#2]\",\n      \"Plasmoredoxin (Plrx) — interactor identified by affinity trapping [#2]\"\n    ],\n    \"other_free_text\": [\n      \"Inhibited by the ornithine analogue canaline (Ki ~492 nM) [#1]\",\n      \"Plasmodium-specific active-site cysteines Cys154 and Cys163 mediate thioredoxin-dependent redox activation; Cys154 also required for ornithine binding/activity [#3]\",\n      \"OAT-mediated glutamine-to-ornithine flux is quantitatively minor in P. falciparum [#1]\",\n      \"OAT is explicitly not the genetic driver of the adaptive proline response to prolyl-tRNA synthetase inhibitors [#4]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0608800","name":null,"product":"ornithine aminotransferase","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0107400","name":null,"product":"ornithine aminotransferase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1141400","name":null,"product":"ornithine aminotransferase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"OAT","evaluation":null}