{"gene":"PF3D7_1353900","run_date":"2026-09-08T14:19:06","timeline":{"discoveries":[{"year":2016,"finding":"PF3D7_1353900 (proteasome subunit alpha type-7) is a structural component of the P. falciparum 20S proteasome (Pf20S) complex, whose overall architecture was resolved by cryo-EM to 3.6 Å; no specific mechanistic role was assigned to this alpha subunit beyond its presence in the complex.","method":"Cryo-electron microscopy and single-particle analysis of the intact Pf20S complex","journal":"Nature","confidence":"Low","confidence_rationale":"Tier 2 / Weak — structure of the whole complex established membership of alpha subunits, but no finding was attributed specifically to PF3D7_1353900","pmids":["26863983"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"finding":"PF3D7_1353900 (proteasome alpha type-7 subunit) is part of the Pf20S alpha ring; cryo-EM structures of Pf20S capped with PfPA28 at 3.8–3.9 Å resolution show that PfPA28 binds the alpha ring asymmetrically, strongly engaging subunits on only one face of the 20S core, implicating the alpha ring (including alpha type-7) in regulator binding, but no specific function was assigned to this individual subunit.","method":"Single-particle cryo-EM of Pf20S–PfPA28 complex; crystal structure of PfPA28; molecular dynamics simulations","journal":"Nature microbiology","confidence":"Low","confidence_rationale":"Tier 2 / Weak — high-resolution structural data on the intact complex, but no finding specific to PF3D7_1353900 as an individual subunit","pmids":["31384003"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1353900 (proteasome subunit alpha type-7) is established only as a structural component of the P. falciparum 20S proteasome complex; no specific catalytic activity, binding partners, post-translational modifications, or individual functional role have been assigned to this subunit in the available literature."},"narrative":{"mechanistic_narrative":"PF3D7_1353900 (proteasome subunit alpha type-7, putative) is established in the available corpus only as a structural alpha-ring component of the P. falciparum 20S proteasome (Pf20S), whose intact architecture was resolved by cryo-EM to 3.6 Å [PMID:26863983]. As part of the Pf20S alpha ring, it lies at the face engaged by the regulator PfPA28, which binds the alpha ring asymmetrically in cryo-EM structures of the Pf20S–PfPA28 complex, implicating the alpha ring in regulator docking [PMID:31384003]. No catalytic activity, binding partner, post-translational modification, or individual functional role has been attributed specifically to PF3D7_1353900 beyond its membership in the 20S core in the available corpus.","teleology":[{"year":2016,"claim":"Before the Pf20S structure it was unclear how the parasite 20S core was organized; resolving the intact complex placed PF3D7_1353900 as one of the alpha-ring structural subunits.","evidence":"Cryo-EM single-particle analysis of the intact Pf20S complex at 3.6 Å","pmids":["26863983"],"confidence":"Low","gaps":["No function attributed specifically to PF3D7_1353900 beyond presence in the complex","No catalytic role assigned to this alpha subunit","No individual binding partners or PTMs identified"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"claim":"How regulators engage the Pf20S alpha ring was unknown; structures of the Pf20S–PfPA28 complex showed asymmetric PfPA28 binding to the alpha ring, implicating alpha-ring subunits including alpha type-7 in regulator docking.","evidence":"Single-particle cryo-EM of Pf20S–PfPA28 at 3.8–3.9 Å, crystal structure of PfPA28, and molecular dynamics simulations","pmids":["31384003"],"confidence":"Low","gaps":["No contribution attributed specifically to PF3D7_1353900 within the alpha ring","Functional consequence of PfPA28 engagement for this subunit not defined","No direct interaction interface mapped for this individual subunit"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether PF3D7_1353900 has any subunit-specific role, catalytic contribution, regulatory function, or distinct binding partner beyond being an alpha-ring structural component remains uncharacterized in the available corpus.","evidence":"","pmids":[],"confidence":"Low","gaps":["No individual functional assignment to PF3D7_1353900","No genetic or biochemical perturbation of this specific subunit","No subunit-specific interactome or PTM data"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["P. falciparum 20S proteasome (Pf20S) core complex","Pf20S–PfPA28 complex"],"partners":[],"other_free_text":["Structural alpha-ring subunit of the Pf20S 20S proteasome core [#0]","Alpha ring is the face engaged asymmetrically by the regulator PfPA28 [#1]","No catalytic activity, binding partner, PTM, or subunit-specific function assigned to PF3D7_1353900 in the available corpus"]}},"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":1072,"usd":0.017236,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5198,"output_tokens":1365,"usd":0.030058,"stage2_stop_reason":"end_turn"},"total_usd":0.047294,"stage1_batch_id":"msgbatch_011BPjN2BL33F8cJXD1r7V7T","stage2_batch_id":"msgbatch_01Qwg6vP7qxkpL6Gsc7tajsb","note":"batch pricing = 50% of standard"},"stage1_raw":"Looking at these papers, I need to determine what they establish specifically about PF3D7_1353900 (proteasome subunit alpha type-7) versus the broader P. falciparum 20S proteasome complex.\n\nAll 7 papers are about the P. falciparum 20S proteasome (Pf20S) as a drug target. They focus on the **beta subunits** (β2, β5, β6, β7) as active sites and inhibitor targets. Alpha subunits (like alpha type-7, PF3D7_1353900) form the structural outer rings of the 20S proteasome but are not the catalytic subunits being discussed.\n\nThe cryo-EM structures in papers [1], [3], [4], [5], [6], [7] resolve the Pf20S complex, which would include the alpha subunits as structural components. Paper [3] specifically notes \"PfPA28 binds Pf20S asymmetrically, strongly engaging subunits on only one side of the core\" — this involves alpha ring subunits structurally.\n\nHowever, none of these abstracts specifically identify or characterize PF3D7_1353900 (alpha type-7 subunit) by name or by its specific role. The papers establish PF3D7_1353900's membership in the 20S proteasome complex (as it's an alpha subunit), but no abstract singles it out for mechanistic characterization. I cannot attribute findings about beta subunit active sites to this alpha subunit.\n\nThe only valid extraction is that PF3D7_1353900, as a proteasome alpha subunit, is a structural component of the Pf20S complex — but no abstract establishes anything mechanistic specifically about this subunit beyond complex membership.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2016,\n      \"finding\": \"PF3D7_1353900 (proteasome subunit alpha type-7) is a structural component of the P. falciparum 20S proteasome (Pf20S) complex, whose overall architecture was resolved by cryo-EM to 3.6 Å; no specific mechanistic role was assigned to this alpha subunit beyond its presence in the complex.\",\n      \"method\": \"Cryo-electron microscopy and single-particle analysis of the intact Pf20S complex\",\n      \"journal\": \"Nature\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 2 / Weak — structure of the whole complex established membership of alpha subunits, but no finding was attributed specifically to PF3D7_1353900\",\n      \"pmids\": [\"26863983\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"PF3D7_1353900 (proteasome alpha type-7 subunit) is part of the Pf20S alpha ring; cryo-EM structures of Pf20S capped with PfPA28 at 3.8–3.9 Å resolution show that PfPA28 binds the alpha ring asymmetrically, strongly engaging subunits on only one face of the 20S core, implicating the alpha ring (including alpha type-7) in regulator binding, but no specific function was assigned to this individual subunit.\",\n      \"method\": \"Single-particle cryo-EM of Pf20S–PfPA28 complex; crystal structure of PfPA28; molecular dynamics simulations\",\n      \"journal\": \"Nature microbiology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 2 / Weak — high-resolution structural data on the intact complex, but no finding specific to PF3D7_1353900 as an individual subunit\",\n      \"pmids\": [\"31384003\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_1353900 (proteasome subunit alpha type-7) is established only as a structural component of the P. falciparum 20S proteasome complex; no specific catalytic activity, binding partners, post-translational modifications, or individual functional role have been assigned to this subunit in the available literature.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1353900 (proteasome subunit alpha type-7, putative) is established in the available corpus only as a structural alpha-ring component of the P. falciparum 20S proteasome (Pf20S), whose intact architecture was resolved by cryo-EM to 3.6 Å [#0]. As part of the Pf20S alpha ring, it lies at the face engaged by the regulator PfPA28, which binds the alpha ring asymmetrically in cryo-EM structures of the Pf20S–PfPA28 complex, implicating the alpha ring in regulator docking [#1]. No catalytic activity, binding partner, post-translational modification, or individual functional role has been attributed specifically to PF3D7_1353900 beyond its membership in the 20S core in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2016,\n      \"claim\": \"Before the Pf20S structure it was unclear how the parasite 20S core was organized; resolving the intact complex placed PF3D7_1353900 as one of the alpha-ring structural subunits.\",\n      \"evidence\": \"Cryo-EM single-particle analysis of the intact Pf20S complex at 3.6 Å\",\n      \"pmids\": [\"26863983\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No function attributed specifically to PF3D7_1353900 beyond presence in the complex\",\n        \"No catalytic role assigned to this alpha subunit\",\n        \"No individual binding partners or PTMs identified\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"How regulators engage the Pf20S alpha ring was unknown; structures of the Pf20S–PfPA28 complex showed asymmetric PfPA28 binding to the alpha ring, implicating alpha-ring subunits including alpha type-7 in regulator docking.\",\n      \"evidence\": \"Single-particle cryo-EM of Pf20S–PfPA28 at 3.8–3.9 Å, crystal structure of PfPA28, and molecular dynamics simulations\",\n      \"pmids\": [\"31384003\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No contribution attributed specifically to PF3D7_1353900 within the alpha ring\",\n        \"Functional consequence of PfPA28 engagement for this subunit not defined\",\n        \"No direct interaction interface mapped for this individual subunit\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether PF3D7_1353900 has any subunit-specific role, catalytic contribution, regulatory function, or distinct binding partner beyond being an alpha-ring structural component remains uncharacterized in the available corpus.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No individual functional assignment to PF3D7_1353900\",\n        \"No genetic or biochemical perturbation of this specific subunit\",\n        \"No subunit-specific interactome or PTM data\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [],\n    \"complexes\": [\"P. falciparum 20S proteasome (Pf20S) core complex\", \"Pf20S–PfPA28 complex\"],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"Structural alpha-ring subunit of the Pf20S 20S proteasome core [#0]\",\n      \"Alpha ring is the face engaged asymmetrically by the regulator PfPA28 [#1]\",\n      \"No catalytic activity, binding partner, PTM, or subunit-specific function assigned to PF3D7_1353900 in the available corpus\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_1353900","tier":"IDENTITY_CHECK","verdict":"identity unverified","subtype":"names_other_cards","uniprot_band":"","rules_fired":"R12","issue":"No cited paper names this card; 1 of 2 cited papers name other catalogue genes (PF3D7_0907700). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1353900","name":null,"product":"proteasome subunit alpha type-7, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1130500","name":null,"product":"proteasome subunit alpha type-7, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1117800","name":null,"product":"proteasome subunit alpha type-7, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}