{"gene":"PF3D7_1459700","run_date":"2026-09-08T14:19:07","timeline":{"discoveries":[{"year":2005,"finding":"PfPdx1 (PF3D7_1459700) functions as the pyridoxal 5'-phosphate (PLP) synthase catalytic domain within a heteromeric complex with PfPdx2; complex formation is required for catalytic activity of either domain, with PfPdx2 acting as the glutaminase subunit providing ammonia to PfPdx1.","method":"Recombinant protein expression, in vitro enzyme activity assays, co-complex reconstitution","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro reconstitution of the complex, enzymatic activity assays demonstrating requirement for complex formation, supported by structural data on PfPdx2","pmids":["16339145"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2005,"finding":"PfPdx1 forms a chimeric bi-enzyme complex with bacterial YaaE (a Pdx2 ortholog) both in vivo and in vitro, but this chimera does not attain full catalytic activity, demonstrating that species-specific structural features govern Pdx1–Pdx2 interaction.","method":"In vivo and in vitro chimeric complex formation assays, enzyme activity measurement","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reconstitution in two systems (in vivo and in vitro), single lab","pmids":["16339145"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2005,"finding":"Blood-stage P. falciparum parasites possess a functional vitamin B6 de novo biosynthesis pathway involving PfPdx1 and PfPdx2, as shown by expression profiling of both proteins in blood-stage parasites.","method":"Expression profiling and recombinant protein biochemical characterization","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — expression profiling combined with biochemical activity demonstration, single lab","pmids":["16339145"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"finding":"The C-terminus of PfPdx1 has four distinct functions: assembly of Pdx1 monomers into the dodecameric complex, binding of the pentose substrate ribose 5-phosphate (R5P), formation of the reaction intermediate I320, and PLP synthesis. Only PLP formation is conferred by the C-terminus acting in trans, explaining the cooperative nature of the complex.","method":"C-terminal deletion analysis, enzyme activity assays, detection of reaction intermediates","journal":"FEBS letters","confidence":"Medium","confidence_rationale":"Tier 1 / Moderate — systematic deletion analysis with multiple functional readouts, single lab","pmids":["20837012"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"finding":"PfPdx1 condenses ammonia (from PfPdx2), R5P, and G3P via a series of imine bond formations to produce PLP. D-erythrose 4-phosphate (E4P) inhibits PfPdx1 in a dose-dependent manner, and the E4P hydrazide analogue 4PEHz inhibits isolated PfPdx1 with an IC50 of 43 µM and the heteromeric complex with an IC50 of 16 µM.","method":"In vitro enzyme inhibition assays, molecular docking, transgenic parasite overexpression lines","journal":"The Biochemical journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vitro enzyme assays combined with transgenic parasite overexpression rescue confirming on-target activity, single lab","pmids":["23039077"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"finding":"Transgenic P. falciparum lines overexpressing PfPdx1 and PfPdx2 showed protection against the inhibitor 4PEHz, confirming that the PLP synthase complex (including PfPdx1) is the direct intracellular target of this compound.","method":"Transgenic parasite overexpression, in vitro parasite growth inhibition assay","journal":"The Biochemical journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic rescue by overexpression confirms target identity in live parasites, single lab","pmids":["23039077"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1459700 (PfPdx1) is the PLP synthase catalytic subunit of the heteromeric PLP synthase complex in P. falciparum blood-stage parasites; it binds ribose 5-phosphate and glyceraldehyde 3-phosphate and catalyzes a series of imine bond formations to synthesize pyridoxal 5'-phosphate, using ammonia supplied by the glutaminase subunit PfPdx2, with complex formation being obligatory for activity of either subunit, and the C-terminal domain of PfPdx1 uniquely enabling cooperative PLP synthesis in trans."},"narrative":{"mechanistic_narrative":"PF3D7_1459700 (PfPdx1) is the catalytic subunit of the de novo pyridoxal 5'-phosphate (PLP) synthase pathway that supplies vitamin B6 to blood-stage P. falciparum parasites [PMID:16339145]. It condenses ribose 5-phosphate and glyceraldehyde 3-phosphate with ammonia through a series of imine bond formations to synthesize PLP, with the ammonia supplied by the glutaminase subunit PfPdx2; formation of the heteromeric PfPdx1–PfPdx2 complex is obligatory for the catalytic activity of either subunit [PMID:16339145, PMID:23039077]. The C-terminal domain of PfPdx1 carries out four distinct steps — assembly of monomers into the dodecameric complex, binding of the pentose substrate ribose 5-phosphate, formation of the I320 reaction intermediate, and PLP synthesis — with only the final PLP-forming step conferred in trans, accounting for the cooperative behavior of the assembled complex [PMID:20837012]. Species-specific structural features govern the Pdx1–Pdx2 interaction, since a chimeric complex of PfPdx1 with the bacterial Pdx2 ortholog YaaE forms but fails to reach full catalytic activity [PMID:16339145]. The complex is a validated drug target: D-erythrose 4-phosphate inhibits PfPdx1 and its hydrazide analogue 4PEHz inhibits both the isolated enzyme and the heteromeric complex, with overexpression of PfPdx1/PfPdx2 protecting parasites, confirming the PLP synthase complex as the direct intracellular target [PMID:23039077].","teleology":[{"year":2005,"claim":"Established that PfPdx1 is the PLP synthase catalytic subunit and that it requires assembly with the glutaminase subunit PfPdx2 for any activity, defining the enzyme's obligate heteromeric architecture.","evidence":"Recombinant expression, in vitro activity assays, and co-complex reconstitution","pmids":["16339145"],"confidence":"High","gaps":["Stoichiometry and higher-order oligomeric state of the intact complex not resolved here","Kinetic parameters of substrate turnover not quantified"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2005,"claim":"Tested whether the Pdx1–Pdx2 interface is species-specific by pairing PfPdx1 with the bacterial Pdx2 ortholog YaaE, showing the chimera assembles but does not reach full activity.","evidence":"In vivo and in vitro chimeric complex formation and activity measurement","pmids":["16339145"],"confidence":"Medium","gaps":["Structural basis of the interface incompatibility not defined","Single lab, single ortholog pairing tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2005,"claim":"Demonstrated that blood-stage parasites express both PfPdx1 and PfPdx2, establishing that de novo vitamin B6 biosynthesis is operative at the clinically relevant stage.","evidence":"Expression profiling combined with recombinant biochemical characterization","pmids":["16339145"],"confidence":"Medium","gaps":["Contribution of de novo synthesis versus salvage to parasite B6 pools not quantified","Stage-specific requirement not tested by genetic knockout"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"claim":"Dissected the multifunctional C-terminus of PfPdx1, resolving how monomer assembly, R5P binding, intermediate formation, and PLP synthesis are partitioned and why only the final step acts in trans.","evidence":"C-terminal deletion analysis with enzyme activity assays and reaction-intermediate detection","pmids":["20837012"],"confidence":"Medium","gaps":["Residue-level catalytic mechanism of the trans PLP-forming step not defined","No crystal structure of the assembled PfPdx1 dodecamer provided"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"claim":"Defined the full condensation chemistry (ammonia + R5P + G3P via imine bonds) and identified E4P and its hydrazide analogue 4PEHz as inhibitors, opening a route to pharmacological targeting.","evidence":"In vitro enzyme inhibition assays, molecular docking, and transgenic overexpression lines","pmids":["23039077"],"confidence":"Medium","gaps":["Inhibitor selectivity over host enzymes not established","IC50 values in the micromolar range leave potency to be improved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"claim":"Confirmed the PLP synthase complex as the direct intracellular target of 4PEHz by showing PfPdx1/PfPdx2 overexpression rescues parasites from the inhibitor.","evidence":"Transgenic parasite overexpression with in vitro growth inhibition assay","pmids":["23039077"],"confidence":"Medium","gaps":["Whether inhibition is essential for parasite killing across all stages not tested","Single lab genetic rescue"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The in vivo essentiality of PfPdx1 by direct genetic knockout, its cellular localization, and the atomic structure of the assembled Plasmodium complex remain uncharacterized in the available corpus.","evidence":"","pmids":[],"confidence":"Low","gaps":["No loss-of-function knockout establishing essentiality","No subcellular localization data","No high-resolution structure of the PfPdx1 dodecamer or PfPdx1–PfPdx2 complex"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PLP synthase complex (PfPdx1 catalytic subunit + PfPdx2 glutaminase subunit)","Dodecameric PfPdx1 assembly"],"partners":["PFPDX2 (GLUTAMINASE SUBUNIT, AMMONIA DONOR)","YAAE (BACTERIAL PDX2 ORTHOLOG; CHIMERIC PARTNER, IN VITRO/IN VIVO)"],"other_free_text":["Catalyzes PLP synthesis by condensing ribose 5-phosphate, glyceraldehyde 3-phosphate, and ammonia through imine bond formation [#4].","C-terminal domain partitions four functions — complex assembly, R5P binding, I320 intermediate formation, and PLP synthesis — with only PLP synthesis acting in trans, explaining cooperativity [#3].","Complex formation with PfPdx2 is obligatory for activity of either subunit [#0].","Inhibited by D-erythrose 4-phosphate; the hydrazide analogue 4PEHz inhibits isolated PfPdx1 (IC50 43 µM) and the heteromeric complex (IC50 16 µM), and is validated as targeting the complex in live parasites via overexpression rescue [#4, #5]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"16339145","id":"PMC_16339145","title":"Vitamin B6 biosynthesis by the malaria parasite Plasmodium falciparum: biochemical and structural insights.","date":"2005","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/16339145","citation_count":65,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["pyridoxal 5'-phosphate synthase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"23039077","id":"PMC_23039077","title":"Exploring inhibition of Pdx1, a component of the PLP synthase complex of the human malaria parasite Plasmodium falciparum.","date":"2013","source":"The Biochemical journal","url":"https://pubmed.ncbi.nlm.nih.gov/23039077","citation_count":13,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["pyridoxal 5'-phosphate synthase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"20837012","id":"PMC_20837012","title":"Defining the structural requirements for ribose 5-phosphate-binding and intersubunit cross-talk of the malarial pyridoxal 5-phosphate synthase.","date":"2010","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/20837012","citation_count":6,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["pyridoxal 5'-phosphate synthase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"31626961","id":"PMC_31626961","title":"Improved stability of polyclonal antibodies: A case study with lyophilization-conserved antibodies raised against epitopes from the malaria parasite Plasmodium falciparum.","date":"2019","source":"European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences","url":"https://pubmed.ncbi.nlm.nih.gov/31626961","citation_count":4,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["pyridoxal 5'-phosphate synthase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"42305886","id":"PMC_42305886","title":"Biological activity of Juglans regia leaf extract and in silico evaluation of its phytochemicals against Plasmodium berghei target proteins.","date":"2026","source":"Helminthologia","url":"https://pubmed.ncbi.nlm.nih.gov/42305886","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["pyridoxal 5'-phosphate synthase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5581,"output_tokens":1584,"usd":0.020251,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6603,"output_tokens":2898,"usd":0.052733,"stage2_stop_reason":"end_turn"},"total_usd":0.072984,"stage1_batch_id":"msgbatch_011BPjN2BL33F8cJXD1r7V7T","stage2_batch_id":"msgbatch_01Qwg6vP7qxkpL6Gsc7tajsb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2005,\n      \"finding\": \"PfPdx1 (PF3D7_1459700) functions as the pyridoxal 5'-phosphate (PLP) synthase catalytic domain within a heteromeric complex with PfPdx2; complex formation is required for catalytic activity of either domain, with PfPdx2 acting as the glutaminase subunit providing ammonia to PfPdx1.\",\n      \"method\": \"Recombinant protein expression, in vitro enzyme activity assays, co-complex reconstitution\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro reconstitution of the complex, enzymatic activity assays demonstrating requirement for complex formation, supported by structural data on PfPdx2\",\n      \"pmids\": [\"16339145\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"PfPdx1 forms a chimeric bi-enzyme complex with bacterial YaaE (a Pdx2 ortholog) both in vivo and in vitro, but this chimera does not attain full catalytic activity, demonstrating that species-specific structural features govern Pdx1–Pdx2 interaction.\",\n      \"method\": \"In vivo and in vitro chimeric complex formation assays, enzyme activity measurement\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reconstitution in two systems (in vivo and in vitro), single lab\",\n      \"pmids\": [\"16339145\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"Blood-stage P. falciparum parasites possess a functional vitamin B6 de novo biosynthesis pathway involving PfPdx1 and PfPdx2, as shown by expression profiling of both proteins in blood-stage parasites.\",\n      \"method\": \"Expression profiling and recombinant protein biochemical characterization\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — expression profiling combined with biochemical activity demonstration, single lab\",\n      \"pmids\": [\"16339145\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"The C-terminus of PfPdx1 has four distinct functions: assembly of Pdx1 monomers into the dodecameric complex, binding of the pentose substrate ribose 5-phosphate (R5P), formation of the reaction intermediate I320, and PLP synthesis. Only PLP formation is conferred by the C-terminus acting in trans, explaining the cooperative nature of the complex.\",\n      \"method\": \"C-terminal deletion analysis, enzyme activity assays, detection of reaction intermediates\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — systematic deletion analysis with multiple functional readouts, single lab\",\n      \"pmids\": [\"20837012\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"PfPdx1 condenses ammonia (from PfPdx2), R5P, and G3P via a series of imine bond formations to produce PLP. D-erythrose 4-phosphate (E4P) inhibits PfPdx1 in a dose-dependent manner, and the E4P hydrazide analogue 4PEHz inhibits isolated PfPdx1 with an IC50 of 43 µM and the heteromeric complex with an IC50 of 16 µM.\",\n      \"method\": \"In vitro enzyme inhibition assays, molecular docking, transgenic parasite overexpression lines\",\n      \"journal\": \"The Biochemical journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vitro enzyme assays combined with transgenic parasite overexpression rescue confirming on-target activity, single lab\",\n      \"pmids\": [\"23039077\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Transgenic P. falciparum lines overexpressing PfPdx1 and PfPdx2 showed protection against the inhibitor 4PEHz, confirming that the PLP synthase complex (including PfPdx1) is the direct intracellular target of this compound.\",\n      \"method\": \"Transgenic parasite overexpression, in vitro parasite growth inhibition assay\",\n      \"journal\": \"The Biochemical journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic rescue by overexpression confirms target identity in live parasites, single lab\",\n      \"pmids\": [\"23039077\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_1459700 (PfPdx1) is the PLP synthase catalytic subunit of the heteromeric PLP synthase complex in P. falciparum blood-stage parasites; it binds ribose 5-phosphate and glyceraldehyde 3-phosphate and catalyzes a series of imine bond formations to synthesize pyridoxal 5'-phosphate, using ammonia supplied by the glutaminase subunit PfPdx2, with complex formation being obligatory for activity of either subunit, and the C-terminal domain of PfPdx1 uniquely enabling cooperative PLP synthesis in trans.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1459700 (PfPdx1) is the catalytic subunit of the de novo pyridoxal 5'-phosphate (PLP) synthase pathway that supplies vitamin B6 to blood-stage P. falciparum parasites [#0, #2]. It condenses ribose 5-phosphate and glyceraldehyde 3-phosphate with ammonia through a series of imine bond formations to synthesize PLP, with the ammonia supplied by the glutaminase subunit PfPdx2; formation of the heteromeric PfPdx1–PfPdx2 complex is obligatory for the catalytic activity of either subunit [#0, #4]. The C-terminal domain of PfPdx1 carries out four distinct steps — assembly of monomers into the dodecameric complex, binding of the pentose substrate ribose 5-phosphate, formation of the I320 reaction intermediate, and PLP synthesis — with only the final PLP-forming step conferred in trans, accounting for the cooperative behavior of the assembled complex [#3]. Species-specific structural features govern the Pdx1–Pdx2 interaction, since a chimeric complex of PfPdx1 with the bacterial Pdx2 ortholog YaaE forms but fails to reach full catalytic activity [#1]. The complex is a validated drug target: D-erythrose 4-phosphate inhibits PfPdx1 and its hydrazide analogue 4PEHz inhibits both the isolated enzyme and the heteromeric complex, with overexpression of PfPdx1/PfPdx2 protecting parasites, confirming the PLP synthase complex as the direct intracellular target [#4, #5].\",\n  \"teleology\": [\n    {\n      \"year\": 2005,\n      \"claim\": \"Established that PfPdx1 is the PLP synthase catalytic subunit and that it requires assembly with the glutaminase subunit PfPdx2 for any activity, defining the enzyme's obligate heteromeric architecture.\",\n      \"evidence\": \"Recombinant expression, in vitro activity assays, and co-complex reconstitution\",\n      \"pmids\": [\"16339145\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Stoichiometry and higher-order oligomeric state of the intact complex not resolved here\", \"Kinetic parameters of substrate turnover not quantified\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Tested whether the Pdx1–Pdx2 interface is species-specific by pairing PfPdx1 with the bacterial Pdx2 ortholog YaaE, showing the chimera assembles but does not reach full activity.\",\n      \"evidence\": \"In vivo and in vitro chimeric complex formation and activity measurement\",\n      \"pmids\": [\"16339145\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Structural basis of the interface incompatibility not defined\", \"Single lab, single ortholog pairing tested\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Demonstrated that blood-stage parasites express both PfPdx1 and PfPdx2, establishing that de novo vitamin B6 biosynthesis is operative at the clinically relevant stage.\",\n      \"evidence\": \"Expression profiling combined with recombinant biochemical characterization\",\n      \"pmids\": [\"16339145\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Contribution of de novo synthesis versus salvage to parasite B6 pools not quantified\", \"Stage-specific requirement not tested by genetic knockout\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Dissected the multifunctional C-terminus of PfPdx1, resolving how monomer assembly, R5P binding, intermediate formation, and PLP synthesis are partitioned and why only the final step acts in trans.\",\n      \"evidence\": \"C-terminal deletion analysis with enzyme activity assays and reaction-intermediate detection\",\n      \"pmids\": [\"20837012\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Residue-level catalytic mechanism of the trans PLP-forming step not defined\", \"No crystal structure of the assembled PfPdx1 dodecamer provided\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Defined the full condensation chemistry (ammonia + R5P + G3P via imine bonds) and identified E4P and its hydrazide analogue 4PEHz as inhibitors, opening a route to pharmacological targeting.\",\n      \"evidence\": \"In vitro enzyme inhibition assays, molecular docking, and transgenic overexpression lines\",\n      \"pmids\": [\"23039077\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Inhibitor selectivity over host enzymes not established\", \"IC50 values in the micromolar range leave potency to be improved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Confirmed the PLP synthase complex as the direct intracellular target of 4PEHz by showing PfPdx1/PfPdx2 overexpression rescues parasites from the inhibitor.\",\n      \"evidence\": \"Transgenic parasite overexpression with in vitro growth inhibition assay\",\n      \"pmids\": [\"23039077\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether inhibition is essential for parasite killing across all stages not tested\", \"Single lab genetic rescue\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The in vivo essentiality of PfPdx1 by direct genetic knockout, its cellular localization, and the atomic structure of the assembled Plasmodium complex remain uncharacterized in the available corpus.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No loss-of-function knockout establishing essentiality\", \"No subcellular localization data\", \"No high-resolution structure of the PfPdx1 dodecamer or PfPdx1–PfPdx2 complex\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0036381\", \"supporting_discovery_ids\": [0, 3, 4]},\n      {\"term_id\": \"GO:0016597\", \"supporting_discovery_ids\": [3, 4]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0042823\", \"supporting_discovery_ids\": [0, 2, 4]}\n    ],\n    \"complexes\": [\n      \"PLP synthase complex (PfPdx1 catalytic subunit + PfPdx2 glutaminase subunit)\",\n      \"Dodecameric PfPdx1 assembly\"\n    ],\n    \"partners\": [\n      \"PfPdx2 (glutaminase subunit, ammonia donor)\",\n      \"YaaE (bacterial Pdx2 ortholog; chimeric partner, in vitro/in vivo)\"\n    ],\n    \"other_free_text\": [\n      \"Catalyzes PLP synthesis by condensing ribose 5-phosphate, glyceraldehyde 3-phosphate, and ammonia through imine bond formation [#4].\",\n      \"C-terminal domain partitions four functions — complex assembly, R5P binding, I320 intermediate formation, and PLP synthesis — with only PLP synthesis acting in trans, explaining cooperativity [#3].\",\n      \"Complex formation with PfPdx2 is obligatory for activity of either subunit [#0].\",\n      \"Inhibited by D-erythrose 4-phosphate; the hydrazide analogue 4PEHz inhibits isolated PfPdx1 (IC50 43 µM) and the heteromeric complex (IC50 16 µM), and is validated as targeting the complex in live parasites via overexpression rescue [#4, #5].\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_1459700","tier":"IDENTITY_CHECK","verdict":"identity unverified","subtype":"names_other_cards","uniprot_band":"","rules_fired":"R12","issue":"No cited paper names this card; 3 of 3 cited papers name other catalogue genes (PF3D7_0621200, PF3D7_1116200). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1459700","name":null,"product":"pyridoxal 5'-phosphate synthase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1323300","name":null,"product":"pyridoxal 5'-phosphate synthase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1222100","name":null,"product":"pyridoxal 5'-phosphate synthase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}