{"gene":"PF3D7_1435000","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2024,"finding":"A photoactivatable derivative of 9-methoxystrobilurin G (9MG), used in chemoproteomic-based target profiling, specifically enriched COX15 (PF3D7_1435000) along with QCR7 and QCR9, identifying COX15 as a component of mitochondrial complex III physically associated with the 9MG target site in P. falciparum. Resistance mutations independently mapped to cytochrome b (complex III), consistent with COX15 being part of the complex III functional unit.","method":"Chemoproteomic target profiling using a photoactivatable 9MG derivative (chemical pulldown/enrichment) combined with genome sequencing of drug-resistant clones and ubiquinone cytochrome c reductase activity assay","journal":"Molecular omics","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single chemoproteomic pulldown experiment; COX15 enrichment is consistent with complex III association but no direct functional characterization of COX15 itself was performed","pmids":["39262389"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":"3D7"},{"species":"Plasmodium falciparum","strain":"Dd2"}]}],"current_model":"PF3D7_1435000 (COX15) has been identified as a component of mitochondrial complex III in P. falciparum by chemoproteomic enrichment, but no direct enzymatic activity, structural data, or specific functional characterization of COX15 itself has been established."},"narrative":{"mechanistic_narrative":"PF3D7_1435000 (COX15) has been experimentally implicated only as a component physically associated with the mitochondrial electron-transport machinery in Plasmodium falciparum. In a chemoproteomic target-profiling study, a photoactivatable derivative of 9-methoxystrobilurin G enriched COX15 together with QCR7 and QCR9, placing COX15 at or near the inhibitor's binding site within the complex III functional unit; resistance mutations mapping independently to cytochrome b reinforced this complex III association [PMID:39262389]. Beyond this enrichment-based assignment [PMID:39262389], no direct enzymatic activity, substrate, structural model, or dedicated functional characterization of COX15 itself has been established in the available corpus.","teleology":[{"year":2024,"claim":"To identify the molecular targets of the antimalarial strobilurin 9-methoxystrobilurin G, chemoproteomic profiling asked which parasite proteins sit at the inhibitor binding site — and this placed COX15 within the mitochondrial complex III functional unit.","evidence":"Chemical pulldown/enrichment with a photoactivatable 9MG derivative, plus genome sequencing of drug-resistant clones and a ubiquinone cytochrome c reductase activity assay, in P. falciparum 3D7 and Dd2","pmids":["39262389"],"confidence":"Low","gaps":["Single chemoproteomic pulldown from one lab; COX15 enrichment indicates proximity/association but was not independently confirmed","No direct enzymatic activity, substrate, or catalytic role for COX15 itself was demonstrated","Resistance mutations mapped to cytochrome b, not to COX15, leaving COX15's specific contribution to the complex undefined"],"attribution":[{"species":"Plasmodium falciparum","strain":"3D7"},{"species":"Plasmodium falciparum","strain":"Dd2"}]},{"year":null,"claim":"Whether COX15 has an intrinsic enzymatic or assembly function, its structure, and its specific role within the mitochondrial electron-transport complex remain uncharacterized.","evidence":"No direct functional experiment on COX15 exists in the available corpus","pmids":[],"confidence":"Low","gaps":["No structural model or defined molecular activity for COX15","No genetic knockout/knockdown phenotype establishing its cellular role","Its precise position and function within the complex III functional unit are undefined"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Mitochondrial complex III functional unit (association inferred from chemoproteomic enrichment) [#0]"],"partners":["QCR7 (CO-ENRICHED) [#0]","QCR9 (CO-ENRICHED) [#0]"],"other_free_text":["COX15 (PF3D7_1435000) was enriched by a photoactivatable 9-methoxystrobilurin G probe, placing it at or near the inhibitor binding site of complex III in P. falciparum [#0]","Resistance mutations to 9MG mapped independently to cytochrome b, consistent with COX15 being part of the complex III functional unit rather than the drug-resistance locus itself [#0]","No direct enzymatic, structural, or functional characterization of COX15 itself is present in the corpus [#0]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"39262389","id":"PMC_39262389","title":"Antimalarial mechanism of action of the natural product 9-methoxystrobilurin G.","date":"2024","source":"Molecular omics","url":"https://pubmed.ncbi.nlm.nih.gov/39262389","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["COX15"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"37594630","id":"","title":"Protease-independent control of parthanatos by HtrA2/Omi.","date":"2023","source":"Cellular and molecular life sciences : CMLS","url":"https://pubmed.ncbi.nlm.nih.gov/37594630","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["COX15"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5045,"output_tokens":457,"usd":0.010995,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":4970,"output_tokens":1276,"usd":0.028375,"stage2_stop_reason":"end_turn"},"total_usd":0.03937,"stage1_batch_id":"msgbatch_01SRp5hyRc82zNjddxyCCXGk","stage2_batch_id":"msgbatch_01K3BTmBazRo3pRrMvyaPMTY","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2024,\n      \"finding\": \"A photoactivatable derivative of 9-methoxystrobilurin G (9MG), used in chemoproteomic-based target profiling, specifically enriched COX15 (PF3D7_1435000) along with QCR7 and QCR9, identifying COX15 as a component of mitochondrial complex III physically associated with the 9MG target site in P. falciparum. Resistance mutations independently mapped to cytochrome b (complex III), consistent with COX15 being part of the complex III functional unit.\",\n      \"method\": \"Chemoproteomic target profiling using a photoactivatable 9MG derivative (chemical pulldown/enrichment) combined with genome sequencing of drug-resistant clones and ubiquinone cytochrome c reductase activity assay\",\n      \"journal\": \"Molecular omics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single chemoproteomic pulldown experiment; COX15 enrichment is consistent with complex III association but no direct functional characterization of COX15 itself was performed\",\n      \"pmids\": [\"39262389\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"3D7\"},\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"Dd2\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_1435000 (COX15) has been identified as a component of mitochondrial complex III in P. falciparum by chemoproteomic enrichment, but no direct enzymatic activity, structural data, or specific functional characterization of COX15 itself has been established.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1435000 (COX15) has been experimentally implicated only as a component physically associated with the mitochondrial electron-transport machinery in Plasmodium falciparum. In a chemoproteomic target-profiling study, a photoactivatable derivative of 9-methoxystrobilurin G enriched COX15 together with QCR7 and QCR9, placing COX15 at or near the inhibitor's binding site within the complex III functional unit; resistance mutations mapping independently to cytochrome b reinforced this complex III association [#0]. Beyond this enrichment-based assignment [#0], no direct enzymatic activity, substrate, structural model, or dedicated functional characterization of COX15 itself has been established in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2024,\n      \"claim\": \"To identify the molecular targets of the antimalarial strobilurin 9-methoxystrobilurin G, chemoproteomic profiling asked which parasite proteins sit at the inhibitor binding site — and this placed COX15 within the mitochondrial complex III functional unit.\",\n      \"evidence\": \"Chemical pulldown/enrichment with a photoactivatable 9MG derivative, plus genome sequencing of drug-resistant clones and a ubiquinone cytochrome c reductase activity assay, in P. falciparum 3D7 and Dd2\",\n      \"pmids\": [\"39262389\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single chemoproteomic pulldown from one lab; COX15 enrichment indicates proximity/association but was not independently confirmed\",\n        \"No direct enzymatic activity, substrate, or catalytic role for COX15 itself was demonstrated\",\n        \"Resistance mutations mapped to cytochrome b, not to COX15, leaving COX15's specific contribution to the complex undefined\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"3D7\"},\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"Dd2\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether COX15 has an intrinsic enzymatic or assembly function, its structure, and its specific role within the mitochondrial electron-transport complex remain uncharacterized.\",\n      \"evidence\": \"No direct functional experiment on COX15 exists in the available corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No structural model or defined molecular activity for COX15\",\n        \"No genetic knockout/knockdown phenotype establishing its cellular role\",\n        \"Its precise position and function within the complex III functional unit are undefined\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [],\n    \"complexes\": [\"Mitochondrial complex III functional unit (association inferred from chemoproteomic enrichment) [#0]\"],\n    \"partners\": [\"QCR7 (co-enriched) [#0]\", \"QCR9 (co-enriched) [#0]\"],\n    \"other_free_text\": [\n      \"COX15 (PF3D7_1435000) was enriched by a photoactivatable 9-methoxystrobilurin G probe, placing it at or near the inhibitor binding site of complex III in P. falciparum [#0]\",\n      \"Resistance mutations to 9MG mapped independently to cytochrome b, consistent with COX15 being part of the complex III functional unit rather than the drug-resistance locus itself [#0]\",\n      \"No direct enzymatic, structural, or functional characterization of COX15 itself is present in the corpus [#0]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1435000","name":null,"product":"cytochrome c oxidase assembly protein COX15, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1009800","name":null,"product":"cytochrome c oxidase assembly protein COX15, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0421600","name":null,"product":"cytochrome c oxidase assembly protein COX15, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"COX15","evaluation":null}