{"gene":"PF3D7_1475300","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2022,"finding":"The C-terminal domain of P. falciparum COX11 (PF3D7_1475300) binds copper in vitro, as demonstrated by bicinchoninic acid release assay, atomic absorption spectroscopy, bacterial host growth inhibition assay, ascorbate oxidation inhibition, and thermal shift assay. Site-directed mutagenesis identified cysteine 157 as important for copper binding, while cysteine 60 was not required.","method":"Recombinant expression, in vitro copper binding assays (BCA release, atomic absorption spectroscopy, thermal shift assay), site-directed mutagenesis of cysteine residues, bacterial growth inhibition assay","journal":"Malaria journal","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in vitro biochemical assays with mutagenesis confirming key residue, but single lab and no structural validation or in-parasite functional rescue","pmids":["35672733"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"finding":"Native COX11 (PF3D7_1475300) protein is expressed in P. falciparum, as confirmed by antibodies raised against the recombinant C-terminal domain (rMBPPfCox11Ct).","method":"Antibody detection of native protein (Western blot / immunodetection using polyclonal antibodies against recombinant protein)","journal":"Malaria journal","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — single lab, single immunodetection method confirming native expression","pmids":["35672733"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"P. falciparum COX11 (PF3D7_1475300) is a copper-binding protein whose C-terminal domain binds copper in vitro through a mechanism requiring cysteine 157, and is predicted to transfer copper to the CuB site of cytochrome c oxidase in the parasite mitochondrion."},"narrative":{"mechanistic_narrative":"PF3D7_1475300 (COX11) is a copper-binding protein of Plasmodium falciparum whose C-terminal domain binds copper in vitro, as established through complementary biochemical assays including bicinchoninic acid release, atomic absorption spectroscopy, and thermal shift analysis [PMID:35672733]. Site-directed mutagenesis localized this copper-binding activity to cysteine 157, whereas cysteine 60 was dispensable [PMID:35672733]. The native protein is expressed in P. falciparum, confirmed by antibodies raised against the recombinant C-terminal domain [PMID:35672733]. Beyond in vitro copper binding by its C-terminal domain and confirmation of native expression, no further mechanistic detail — including in-parasite function, copper-transfer activity, or interaction with cytochrome c oxidase — has been characterized in the available corpus.","teleology":[{"year":2022,"claim":"To test whether P. falciparum COX11 functions as a copper-binding protein, its recombinant C-terminal domain was assayed for copper binding, establishing a metal-binding activity attributable to a specific cysteine residue.","evidence":"Recombinant expression with multiple in vitro copper-binding assays (BCA release, atomic absorption spectroscopy, thermal shift) and cysteine mutagenesis","pmids":["35672733"],"confidence":"Medium","gaps":["No structural model of the copper-binding site","No demonstration that copper is transferred to cytochrome c oxidase or the CuB site","No in-parasite functional rescue or knockout to confirm physiological role"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"claim":"To confirm that COX11 is more than a predicted open reading frame, antibodies against the recombinant C-terminal domain detected the native protein, establishing that COX11 is expressed in the parasite.","evidence":"Immunodetection of native protein using polyclonal antibodies raised against recombinant C-terminal domain","pmids":["35672733"],"confidence":"Medium","gaps":["Single immunodetection method without subcellular localization data","Stage-specific expression not characterized","Mitochondrial localization not experimentally demonstrated"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether COX11 transfers copper to cytochrome c oxidase in the parasite mitochondrion and is required for parasite viability remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No in-parasite functional or genetic evidence","No demonstrated interaction with cytochrome c oxidase","No copper-transfer reconstitution"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":["C-terminal domain binds copper in vitro; cysteine 157 required, cysteine 60 dispensable [#0]","Native protein confirmed to be expressed in P. falciparum [#1]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"35672733","id":"PMC_35672733","title":"Expression and copper binding characteristics of Plasmodium falciparum cytochrome c oxidase assembly factor 11, Cox11.","date":"2022","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/35672733","citation_count":3,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["COX11","PfCOX11"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"26881705","id":"","title":"Copper Homeostasis for the Developmental Progression of Intraerythrocytic Malarial Parasite.","date":"2016","source":"Current topics in medicinal chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/26881705","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["COX11"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4402,"output_tokens":622,"usd":0.011268,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5212,"output_tokens":1284,"usd":0.02908,"stage2_stop_reason":"end_turn"},"total_usd":0.040348,"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\": 2022,\n      \"finding\": \"The C-terminal domain of P. falciparum COX11 (PF3D7_1475300) binds copper in vitro, as demonstrated by bicinchoninic acid release assay, atomic absorption spectroscopy, bacterial host growth inhibition assay, ascorbate oxidation inhibition, and thermal shift assay. Site-directed mutagenesis identified cysteine 157 as important for copper binding, while cysteine 60 was not required.\",\n      \"method\": \"Recombinant expression, in vitro copper binding assays (BCA release, atomic absorption spectroscopy, thermal shift assay), site-directed mutagenesis of cysteine residues, bacterial growth inhibition assay\",\n      \"journal\": \"Malaria journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro biochemical assays with mutagenesis confirming key residue, but single lab and no structural validation or in-parasite functional rescue\",\n      \"pmids\": [\"35672733\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Native COX11 (PF3D7_1475300) protein is expressed in P. falciparum, as confirmed by antibodies raised against the recombinant C-terminal domain (rMBPPfCox11Ct).\",\n      \"method\": \"Antibody detection of native protein (Western blot / immunodetection using polyclonal antibodies against recombinant protein)\",\n      \"journal\": \"Malaria journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single immunodetection method confirming native expression\",\n      \"pmids\": [\"35672733\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"P. falciparum COX11 (PF3D7_1475300) is a copper-binding protein whose C-terminal domain binds copper in vitro through a mechanism requiring cysteine 157, and is predicted to transfer copper to the CuB site of cytochrome c oxidase in the parasite mitochondrion.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1475300 (COX11) is a copper-binding protein of Plasmodium falciparum whose C-terminal domain binds copper in vitro, as established through complementary biochemical assays including bicinchoninic acid release, atomic absorption spectroscopy, and thermal shift analysis [#0]. Site-directed mutagenesis localized this copper-binding activity to cysteine 157, whereas cysteine 60 was dispensable [#0]. The native protein is expressed in P. falciparum, confirmed by antibodies raised against the recombinant C-terminal domain [#1]. Beyond in vitro copper binding by its C-terminal domain and confirmation of native expression, no further mechanistic detail — including in-parasite function, copper-transfer activity, or interaction with cytochrome c oxidase — has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2022,\n      \"claim\": \"To test whether P. falciparum COX11 functions as a copper-binding protein, its recombinant C-terminal domain was assayed for copper binding, establishing a metal-binding activity attributable to a specific cysteine residue.\",\n      \"evidence\": \"Recombinant expression with multiple in vitro copper-binding assays (BCA release, atomic absorption spectroscopy, thermal shift) and cysteine mutagenesis\",\n      \"pmids\": [\"35672733\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structural model of the copper-binding site\",\n        \"No demonstration that copper is transferred to cytochrome c oxidase or the CuB site\",\n        \"No in-parasite functional rescue or knockout to confirm physiological role\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"To confirm that COX11 is more than a predicted open reading frame, antibodies against the recombinant C-terminal domain detected the native protein, establishing that COX11 is expressed in the parasite.\",\n      \"evidence\": \"Immunodetection of native protein using polyclonal antibodies raised against recombinant C-terminal domain\",\n      \"pmids\": [\"35672733\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single immunodetection method without subcellular localization data\",\n        \"Stage-specific expression not characterized\",\n        \"Mitochondrial localization not experimentally demonstrated\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether COX11 transfers copper to cytochrome c oxidase in the parasite mitochondrion and is required for parasite viability remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No in-parasite functional or genetic evidence\",\n        \"No demonstrated interaction with cytochrome c oxidase\",\n        \"No copper-transfer reconstitution\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005507\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"C-terminal domain binds copper in vitro; cysteine 157 required, cysteine 60 dispensable [#0]\",\n      \"Native protein confirmed to be expressed in P. falciparum [#1]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1475300","name":null,"product":"cytochrome c oxidase assembly protein COX11, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1300900","name":null,"product":"cytochrome c oxidase assembly protein COX11, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1245600","name":null,"product":"cytochrome c oxidase assembly protein COX11, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"COX11","evaluation":null}