{"gene":"PF3D7_0807500","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2016,"finding":"PF3D7_0807500 (proteasome subunit alpha type-6) is a structural component of the P. falciparum 20S proteasome (Pf20S), whose overall architecture was resolved by cryo-EM to 3.6 Å. No findings specific to the alpha-6 subunit's individual function or mechanism were reported; the subunit's role is inferred solely from its membership in the 20S complex.","method":"Cryo-electron microscopy and single-particle analysis of the Pf20S proteasome complex","journal":"Nature","confidence":"Low","confidence_rationale":"Tier 2 / Weak — high-resolution cryo-EM of the whole complex establishes that alpha subunits are present, but no experiment specifically interrogates PF3D7_0807500 individually; membership inferred from complex membership only","pmids":["26863983"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_0807500 (proteasome subunit alpha type-6) is a structural component of the P. falciparum 20S proteasome; beyond its membership in this essential proteolytic complex, no experiment in the available literature has established a specific mechanistic role for this individual subunit."},"narrative":{"mechanistic_narrative":"PF3D7_0807500 (proteasome subunit alpha type-6, putative) is a structural component of the P. falciparum 20S proteasome (Pf20S), a proteolytic complex whose overall architecture was resolved by cryo-EM to 3.6 Å [PMID:26863983]. Beyond its membership in this complex, no experiment in the available corpus establishes a specific individual function or mechanism for the alpha-6 subunit; its role is inferred solely from its participation in the 20S proteasome [PMID:26863983].","teleology":[{"year":2016,"claim":"Placing PF3D7_0807500 within the P. falciparum 20S proteasome established it as a structural subunit of an essential proteolytic machine, but did not resolve any function unique to this subunit.","evidence":"Cryo-electron microscopy and single-particle analysis of the Pf20S proteasome complex","pmids":["26863983"],"confidence":"Low","gaps":["No experiment interrogates PF3D7_0807500 individually; membership is inferred only from the whole-complex structure","No subunit-specific catalytic, assembly, or regulatory role has been defined","No genetic or biochemical perturbation of this subunit has been reported"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether PF3D7_0807500 contributes any function beyond structural membership in the 20S proteasome remains unknown.","evidence":"","pmids":[],"confidence":"Low","gaps":["No individual functional characterization of the alpha-6 subunit exists in the available corpus","Its specific contribution to Pf20S assembly, stability, or substrate handling is undefined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["P. falciparum 20S proteasome (Pf20S) [#0]"],"partners":[],"other_free_text":["PF3D7_0807500 is assigned as a structural alpha-type subunit of the Pf20S proteasome by cryo-EM at 3.6 Å; no subunit-specific function has been experimentally established in the available corpus [#0]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"26863983","id":"PMC_26863983","title":"Structure- and function-based design of Plasmodium-selective proteasome inhibitors.","date":"2016","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/26863983","citation_count":196,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"24533266","id":"PMC_24533266","title":"The proteasome of malaria parasites: A multi-stage drug target for chemotherapeutic intervention?","date":"2012","source":"International journal for parasitology. Drugs and drug resistance","url":"https://pubmed.ncbi.nlm.nih.gov/24533266","citation_count":64,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"31384003","id":"PMC_31384003","title":"The structure of the PA28-20S proteasome complex from Plasmodium falciparum and implications for proteostasis.","date":"2019","source":"Nature microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/31384003","citation_count":37,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34548400","id":"PMC_34548400","title":"Design of proteasome inhibitors with oral efficacy in vivo against Plasmodium falciparum and selectivity over the human proteasome.","date":"2021","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/34548400","citation_count":33,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38097652","id":"PMC_38097652","title":"Structures revealing mechanisms of resistance and collateral sensitivity of Plasmodium falciparum to proteasome inhibitors.","date":"2023","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/38097652","citation_count":21,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39084225","id":"PMC_39084225","title":"Identification of potent and reversible piperidine carboxamides that are species-selective orally active proteasome inhibitors to treat malaria.","date":"2024","source":"Cell chemical biology","url":"https://pubmed.ncbi.nlm.nih.gov/39084225","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":"41148577","id":"PMC_41148577","title":"Optimization of Species-Selective Reversible Proteasome Inhibitors for the Treatment of Malaria.","date":"2025","source":"Journal of medicinal chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/41148577","citation_count":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6131,"output_tokens":715,"usd":0.014559,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":4813,"output_tokens":908,"usd":0.023383,"stage2_stop_reason":"end_turn"},"total_usd":0.037942,"stage1_batch_id":"msgbatch_01DisAaTypwmC8QwdMBuePHo","stage2_batch_id":"msgbatch_0184zxZTqxiEfdYYfPMfkqjb","note":"batch pricing = 50% of standard"},"stage1_raw":"Looking at the abstracts, I need to determine what mechanistic findings, if any, are specifically about PF3D7_0807500 (proteasome subunit alpha type-6, putative) versus the proteasome complex broadly or other subunits (β2, β5, β6, β7, PA28, etc.).\n\nPF3D7_0807500 is annotated as a **proteasome subunit alpha type-6**. Alpha subunits are structural components of the 20S proteasome outer rings. None of the abstracts specifically call out an alpha-6 subunit by name or by this gene ID. The papers describe:\n- The Pf20S proteasome structure (which includes alpha subunits as part of the complex)\n- Inhibitors targeting β2, β5, β6 active sites\n- PA28 regulator binding to 20S\n- β6 A117D resistance mutations\n\nThe cryo-EM structures (PMIDs 26863983, 34548400, 38097652, 39084225, 41148577) resolve the full 20S complex, which would include alpha-type subunits as structural components, but none specifically characterize the alpha-6 subunit's function or mechanism. PF3D7_0807500 is a structural member of the complex, but none of these abstracts establish anything mechanistically specific to this subunit beyond its membership in the 20S proteasome complex.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2016,\n      \"finding\": \"PF3D7_0807500 (proteasome subunit alpha type-6) is a structural component of the P. falciparum 20S proteasome (Pf20S), whose overall architecture was resolved by cryo-EM to 3.6 Å. No findings specific to the alpha-6 subunit's individual function or mechanism were reported; the subunit's role is inferred solely from its membership in the 20S complex.\",\n      \"method\": \"Cryo-electron microscopy and single-particle analysis of the Pf20S proteasome complex\",\n      \"journal\": \"Nature\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 2 / Weak — high-resolution cryo-EM of the whole complex establishes that alpha subunits are present, but no experiment specifically interrogates PF3D7_0807500 individually; membership inferred from complex membership only\",\n      \"pmids\": [\"26863983\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_0807500 (proteasome subunit alpha type-6) is a structural component of the P. falciparum 20S proteasome; beyond its membership in this essential proteolytic complex, no experiment in the available literature has established a specific mechanistic role for this individual subunit.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0807500 (proteasome subunit alpha type-6, putative) is a structural component of the P. falciparum 20S proteasome (Pf20S), a proteolytic complex whose overall architecture was resolved by cryo-EM to 3.6 Å [#0]. Beyond its membership in this complex, no experiment in the available corpus establishes a specific individual function or mechanism for the alpha-6 subunit; its role is inferred solely from its participation in the 20S proteasome [#0].\",\n  \"teleology\": [\n    {\n      \"year\": 2016,\n      \"claim\": \"Placing PF3D7_0807500 within the P. falciparum 20S proteasome established it as a structural subunit of an essential proteolytic machine, but did not resolve any function unique to this subunit.\",\n      \"evidence\": \"Cryo-electron microscopy and single-particle analysis of the Pf20S proteasome complex\",\n      \"pmids\": [\n        \"26863983\"\n      ],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No experiment interrogates PF3D7_0807500 individually; membership is inferred only from the whole-complex structure\",\n        \"No subunit-specific catalytic, assembly, or regulatory role has been defined\",\n        \"No genetic or biochemical perturbation of this subunit has been reported\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether PF3D7_0807500 contributes any function beyond structural membership in the 20S proteasome remains unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No individual functional characterization of the alpha-6 subunit exists in the available corpus\",\n        \"Its specific contribution to Pf20S assembly, stability, or substrate handling is undefined\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [],\n    \"complexes\": [\n      \"P. falciparum 20S proteasome (Pf20S) [#0]\"\n    ],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"PF3D7_0807500 is assigned as a structural alpha-type subunit of the Pf20S proteasome by cryo-EM at 3.6 Å; no subunit-specific function has been experimentally established in the available corpus [#0].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0807500","name":null,"product":"proteasome subunit alpha type-6, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1223100","name":null,"product":"proteasome subunit alpha type-6, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0111300","name":null,"product":"proteasome subunit alpha type-6, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}