{"gene":"PF3D7_0727400","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2016,"finding":"PF3D7_0727400 (proteasome subunit alpha type-5) is a structural component of the P. falciparum 20S proteasome (Pf20S), whose overall architecture was resolved by cryo-EM at 3.6 Å; however, no specific mechanistic finding was reported for this alpha subunit individually.","method":"Cryo-electron microscopy and single-particle analysis of the intact Pf20S complex","journal":"Nature","confidence":"Low","confidence_rationale":"Tier 3 / Weak — alpha subunit membership inferred from complex structure; no subunit-specific functional or mechanistic data reported for PF3D7_0727400 in the abstract","pmids":["26863983"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_0727400 (proteasome subunit alpha type-5) is a putative structural component of the P. falciparum 20S proteasome complex; no specific mechanistic role, binding partner, post-translational modification, or enzymatic activity has been experimentally established for this individual subunit in the available literature."},"narrative":{"mechanistic_narrative":"PF3D7_0727400 (proteasome subunit alpha type-5, putative) is a structural component of the Plasmodium falciparum 20S proteasome (Pf20S), whose overall architecture was resolved by cryo-EM at 3.6 Å [PMID:26863983]. Beyond this membership in the Pf20S complex, no subunit-specific mechanistic role, binding partner, post-translational modification, or enzymatic activity has been characterized for PF3D7_0727400 individually in the available corpus [PMID:26863983].","teleology":[{"year":2016,"claim":"Establishing the subunit composition and architecture of the P. falciparum 20S proteasome placed PF3D7_0727400 within the assembled Pf20S complex as an alpha-type structural subunit.","evidence":"Cryo-electron microscopy and single-particle analysis of the intact Pf20S complex at 3.6 Å","pmids":["26863983"],"confidence":"Low","gaps":["Alpha subunit membership is inferred from the overall complex structure; no subunit-specific functional or mechanistic data were reported for PF3D7_0727400","No binding partner, post-translational modification, or catalytic contribution has been assigned to this individual subunit","The specific role of PF3D7_0727400 in proteasome assembly, substrate gating, or stability is undetermined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether PF3D7_0727400 has any subunit-specific function distinct from its structural role in the Pf20S complex remains unknown.","evidence":"","pmids":[],"confidence":"Low","gaps":["No experimental data isolate the contribution of PF3D7_0727400 from the intact complex","No essentiality, knockdown, or mutational analysis of this subunit is available","No interaction partners outside the core proteasome have been identified"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["P. falciparum 20S proteasome (Pf20S) [#0]"],"partners":[],"other_free_text":["PF3D7_0727400 is annotated as a putative proteasome subunit alpha type-5 and is placed as a structural alpha subunit within the Pf20S complex resolved by cryo-EM [#0]; no mechanistic property specific to this subunit has been experimentally established."]}},"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":677,"usd":0.014274,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":4777,"output_tokens":969,"usd":0.024055,"stage2_stop_reason":"end_turn"},"total_usd":0.038329,"stage1_batch_id":"msgbatch_01DisAaTypwmC8QwdMBuePHo","stage2_batch_id":"msgbatch_0184zxZTqxiEfdYYfPMfkqjb","note":"batch pricing = 50% of standard"},"stage1_raw":"I need to carefully evaluate these papers. The query gene is PF3D7_0727400, described as \"proteasome subunit alpha type-5, putative\" in P. falciparum.\n\nLooking at the papers:\n- They all describe the P. falciparum 20S proteasome (Pf20S) complex\n- They focus on β-subunits (β2, β5, β6) as the active/catalytic subunits\n- Alpha subunits form the structural rings of the 20S proteasome\n- None of the abstracts specifically mention \"alpha type-5\" or PF3D7_0727400 by name\n\nThe cryo-EM structures of Pf20S would inherently include the alpha subunits (including alpha type-5) as structural components, but none of the abstracts specifically describe findings about this particular alpha subunit's function, binding, or mechanism.\n\nThe most I can establish is that PF3D7_0727400 is a component of the Pf20S proteasome complex (as structural context from the cryo-EM papers), but no abstract makes any specific mechanistic claim about this particular alpha subunit.\n\nI should not adopt the findings about β-subunits and attribute them to this alpha subunit. The papers establish nothing specifically mechanistic about PF3D7_0727400 beyond its implied membership in the Pf20S complex.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2016,\n      \"finding\": \"PF3D7_0727400 (proteasome subunit alpha type-5) is a structural component of the P. falciparum 20S proteasome (Pf20S), whose overall architecture was resolved by cryo-EM at 3.6 Å; however, no specific mechanistic finding was reported for this alpha subunit individually.\",\n      \"method\": \"Cryo-electron microscopy and single-particle analysis of the intact Pf20S complex\",\n      \"journal\": \"Nature\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — alpha subunit membership inferred from complex structure; no subunit-specific functional or mechanistic data reported for PF3D7_0727400 in the abstract\",\n      \"pmids\": [\"26863983\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_0727400 (proteasome subunit alpha type-5) is a putative structural component of the P. falciparum 20S proteasome complex; no specific mechanistic role, binding partner, post-translational modification, or enzymatic activity has been experimentally established for this individual subunit in the available literature.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0727400 (proteasome subunit alpha type-5, putative) is a structural component of the Plasmodium falciparum 20S proteasome (Pf20S), whose overall architecture was resolved by cryo-EM at 3.6 Å [#0]. Beyond this membership in the Pf20S complex, no subunit-specific mechanistic role, binding partner, post-translational modification, or enzymatic activity has been characterized for PF3D7_0727400 individually in the available corpus [#0].\",\n  \"teleology\": [\n    {\n      \"year\": 2016,\n      \"claim\": \"Establishing the subunit composition and architecture of the P. falciparum 20S proteasome placed PF3D7_0727400 within the assembled Pf20S complex as an alpha-type structural subunit.\",\n      \"evidence\": \"Cryo-electron microscopy and single-particle analysis of the intact Pf20S complex at 3.6 Å\",\n      \"pmids\": [\"26863983\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Alpha subunit membership is inferred from the overall complex structure; no subunit-specific functional or mechanistic data were reported for PF3D7_0727400\",\n        \"No binding partner, post-translational modification, or catalytic contribution has been assigned to this individual subunit\",\n        \"The specific role of PF3D7_0727400 in proteasome assembly, substrate gating, or stability is undetermined\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether PF3D7_0727400 has any subunit-specific function distinct from its structural role in the Pf20S complex remains unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No experimental data isolate the contribution of PF3D7_0727400 from the intact complex\",\n        \"No essentiality, knockdown, or mutational analysis of this subunit is available\",\n        \"No interaction partners outside the core proteasome have been identified\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [],\n    \"complexes\": [\"P. falciparum 20S proteasome (Pf20S) [#0]\"],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"PF3D7_0727400 is annotated as a putative proteasome subunit alpha type-5 and is placed as a structural alpha subunit within the Pf20S complex resolved by cryo-EM [#0]; no mechanistic property specific to this subunit has been experimentally established.\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0727400","name":null,"product":"proteasome subunit alpha type-5, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0211500","name":null,"product":"proteasome subunit alpha type-5, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0212000","name":null,"product":"proteasome subunit alpha type-5, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}