{"gene":"PF3D7_0803800","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2000,"finding":"PF3D7_0803800 (a P. falciparum 20S proteasome beta subunit) was molecularly cloned; the gene encodes a 265-amino-acid protein (predicted MW 30.9 kDa, pI 6.2) with a 156-bp intron 85 bp downstream of the start codon, establishing it as a member of the 20S proteasome beta-subunit family.","method":"Molecular cloning, cDNA/genomic DNA sequence comparison, Northern blot","journal":"International journal for parasitology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct cloning and sequence characterization, but only structural/compositional data, no functional assay","pmids":["10856507"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"finding":"Cryo-EM structure of the P. falciparum 20S proteasome (Pf20S) at 3.6 Å resolution placed the beta-subunits (including the beta-type-4 subunit encoded by PF3D7_0803800) within the complex and revealed active-site architecture; the beta2 active site was found to be unusually open compared to the human ortholog, informing subunit-selective inhibitor design.","method":"Cryo-electron microscopy and single-particle analysis at 3.6 Å resolution","journal":"Nature","confidence":"High","confidence_rationale":"Tier 1 / Strong — high-resolution cryo-EM structure of the intact Pf20S complex with bound inhibitor, revealing active-site architecture","pmids":["26863983"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"finding":"Cryo-EM structures of the Pf20S–PfPA28 complex (one and two PA28 caps, resolved at 3.9 Å and 3.8 Å) showed that PA28 binds the 20S core asymmetrically, strongly engaging subunits on only one side; molecular dynamics simulations indicated conformational flexibility at the interface, supporting a lateral-transfer mechanism for release of proteasome degradation products.","method":"Cryo-EM single-particle analysis, crystal structure of PfPA28, SAXS, molecular dynamics simulations, genetic deletion of PA28","journal":"Nature microbiology","confidence":"High","confidence_rationale":"Tier 1 / Strong — multiple orthogonal structural methods (cryo-EM, crystallography, SAXS) plus MD simulations and genetic validation in a single study","pmids":["31384003"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"finding":"Cryo-EM structures of Pf20S and human 20S in complex with amino-amide boronate inhibitor MPI-5, and of Pf20S with bortezomib, revealed differences in beta5 active-site binding modes that explain selectivity of these inhibitors for the parasite proteasome over the human enzyme.","method":"Cryo-EM structure determination, biochemical inhibition assays, resistance profiling","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1 / Strong — high-resolution cryo-EM structures compared across species with biochemical and cellular validation in a single study","pmids":["34548400"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"finding":"High-resolution cryo-EM structures of Pf20S with macrocyclic inhibitor TDI-8304 showed that TDI-8304 binds both the beta2 and beta5 subunits of wild-type Pf20S; a resistance mutation in the beta6 subunit (A117D) eliminates TDI-8304 binding while conferring collateral sensitivity to the beta2 inhibitor WLW-vs, which in the mutant binds both beta2 and beta5.","method":"Cryo-EM structure determination, resistance mutation selection, enzymatic and anti-parasite activity assays","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 1 / Strong — multiple high-resolution cryo-EM structures (wild-type and mutant Pf20S, human 20S) combined with resistance genetics and functional assays","pmids":["38097652"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"finding":"Cryo-EM structure of Pf20S in complex with piperidine carboxamide SW584 revealed non-covalent binding in a previously unexplored pocket at the beta5/beta6/beta3 subunit interface (distal from the catalytic threonine); point mutations in the beta5 active site conferred resistance to SW584, confirming beta5 as the primary pharmacological target.","method":"Cryo-EM structure determination, resistance selection, biochemical inhibition assays, His8-tag proteasome purification","journal":"Cell chemical biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — cryo-EM structure at the subunit interface combined with resistance genetics and biochemical assays in a single study","pmids":["39084225"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_0803800 encodes a beta-type subunit of the P. falciparum 20S proteasome (Pf20S); cryo-EM structures place it within the 20S catalytic core, which assembles with the PA28 regulatory cap asymmetrically and whose beta2, beta5, beta6, and beta3 subunits collectively define species-selective inhibitor-binding pockets that can be exploited for selective antimalarial drug design, while the protein's precise catalytic or structural contribution as the beta-4 subunit specifically has not been individually resolved beyond its membership in the complex."},"narrative":{"mechanistic_narrative":"PF3D7_0803800 encodes a beta-type subunit of the Plasmodium falciparum 20S proteasome (Pf20S), a multi-subunit proteolytic core; the gene was cloned as a 265-amino-acid member of the 20S proteasome beta-subunit family, encoded by a transcript interrupted by a single intron [PMID:10856507]. Cryo-EM structures of the intact Pf20S place this beta-subunit within the assembled catalytic core alongside the other beta-subunits, and reveal active-site architecture in the core that differs from the human enzyme [PMID:26863983]. Within the larger complex, Pf20S associates with the PfPA28 regulatory cap, which engages the 20S core asymmetrically and is consistent with a lateral-transfer mechanism for release of degradation products [PMID:31384003]. The catalytic and inhibitor-binding chemistry of the core has been mapped extensively at the beta2, beta5, beta6, and beta3 subunits, where species-selective pockets are exploited for antimalarial inhibitor design [PMID:34548400, PMID:38097652, PMID:39084225]. Beyond its membership in the Pf20S core established by these structures, the specific catalytic or structural contribution of the PF3D7_0803800 beta-4 subunit as an individual entity has not been resolved in the available corpus.","teleology":[{"year":2000,"claim":"Establishing that P. falciparum possesses this specific proteasome beta-subunit gene defined a candidate component of the parasite's proteolytic machinery at the sequence level.","evidence":"Molecular cloning, cDNA/genomic sequence comparison and Northern blot in P. falciparum","pmids":["10856507"],"confidence":"Medium","gaps":["No functional or catalytic assay for the subunit","Assignment within the assembled complex not shown","Whether the subunit is proteolytically active undetermined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"claim":"The first cryo-EM structure of the intact Pf20S positioned the beta-subunits within the catalytic core and exposed parasite-specific active-site features distinguishing it from the human proteasome.","evidence":"Cryo-EM single-particle analysis at 3.6 Å of the Pf20S complex in P. falciparum","pmids":["26863983"],"confidence":"High","gaps":["Individual catalytic contribution of the beta-4 subunit not isolated","Structure captures the assembled complex, not this subunit in isolation"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"claim":"Resolving how the PfPA28 regulatory cap docks onto the 20S core clarified the architecture and product-release mechanism of the fuller proteasome assembly containing this subunit.","evidence":"Cryo-EM, PfPA28 crystallography, SAXS, molecular dynamics, and PA28 genetic deletion in P. falciparum","pmids":["31384003"],"confidence":"High","gaps":["Role of the beta-4 subunit specifically in PA28 engagement not defined","Functional consequence for this subunit not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"claim":"Comparing Pf20S and human 20S bound to boronate inhibitors explained species selectivity at the beta5 active site, advancing selective antimalarial proteasome inhibitor design.","evidence":"Cryo-EM of Pf20S with MPI-5 and bortezomib plus biochemical inhibition and resistance profiling in P. falciparum","pmids":["34548400"],"confidence":"High","gaps":["Findings center on beta5, not the beta-4 subunit encoded by PF3D7_0803800","No individual functional role for this subunit"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"claim":"Mapping dual beta2/beta5 engagement of TDI-8304 and a beta6 resistance mutation defined how inhibitor binding and collateral sensitivity distribute across core beta-subunits.","evidence":"Cryo-EM of wild-type and mutant Pf20S with resistance selection and enzymatic/anti-parasite assays in P. falciparum","pmids":["38097652"],"confidence":"High","gaps":["Focused on beta2, beta5, beta6, not the beta-4 subunit","No isolated role for PF3D7_0803800"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"claim":"Identifying a non-covalent inhibitor pocket at the beta5/beta6/beta3 interface expanded the druggable surface of the Pf20S core and confirmed beta5 as the primary pharmacological target.","evidence":"Cryo-EM of Pf20S with SW584, resistance selection, and biochemical assays with His8-tag purification in P. falciparum","pmids":["39084225"],"confidence":"High","gaps":["The characterized interface pocket involves beta5/beta6/beta3, not the beta-4 subunit","Contribution of PF3D7_0803800 to this pocket unaddressed"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The individual catalytic or structural role of the PF3D7_0803800 beta-4 subunit, distinct from its membership in the Pf20S core, remains unresolved.","evidence":"No timeline discovery isolates the function of this subunit apart from the assembled complex","pmids":[],"confidence":"Medium","gaps":["No subunit-specific catalytic assay","No inhibitor characterized as binding this subunit specifically","No genetic knockout/knockdown of PF3D7_0803800 alone"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Proteasome 20S core complex (Pf20S)","Pf20S-PfPA28 complex"],"partners":["PFPA28 (PROTEASOME REGULATORY CAP)"],"other_free_text":["Encodes a 265-amino-acid 20S proteasome beta-subunit family member with a single intron [#0]","Positioned within the assembled Pf20S catalytic core by cryo-EM [#1]","Species-selective inhibitor pockets characterized at beta2/beta5/beta6/beta3 subunits of the core, not at the beta-4 subunit specifically [#3, #4, #5]","Individual catalytic/structural role of PF3D7_0803800 as the beta-4 subunit not resolved beyond complex membership"]}},"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":"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":"10856507","id":"PMC_10856507","title":"Molecular cloning of a gene encoding a 20S proteasome beta subunit from Plasmodium falciparum.","date":"2000","source":"International journal for parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/10856507","citation_count":8,"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":5664,"output_tokens":1754,"usd":0.021651,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6786,"output_tokens":2640,"usd":0.049965,"stage2_stop_reason":"end_turn"},"total_usd":0.071616,"stage1_batch_id":"msgbatch_01DisAaTypwmC8QwdMBuePHo","stage2_batch_id":"msgbatch_0184zxZTqxiEfdYYfPMfkqjb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2000,\n      \"finding\": \"PF3D7_0803800 (a P. falciparum 20S proteasome beta subunit) was molecularly cloned; the gene encodes a 265-amino-acid protein (predicted MW 30.9 kDa, pI 6.2) with a 156-bp intron 85 bp downstream of the start codon, establishing it as a member of the 20S proteasome beta-subunit family.\",\n      \"method\": \"Molecular cloning, cDNA/genomic DNA sequence comparison, Northern blot\",\n      \"journal\": \"International journal for parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct cloning and sequence characterization, but only structural/compositional data, no functional assay\",\n      \"pmids\": [\"10856507\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Cryo-EM structure of the P. falciparum 20S proteasome (Pf20S) at 3.6 Å resolution placed the beta-subunits (including the beta-type-4 subunit encoded by PF3D7_0803800) within the complex and revealed active-site architecture; the beta2 active site was found to be unusually open compared to the human ortholog, informing subunit-selective inhibitor design.\",\n      \"method\": \"Cryo-electron microscopy and single-particle analysis at 3.6 Å resolution\",\n      \"journal\": \"Nature\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — high-resolution cryo-EM structure of the intact Pf20S complex with bound inhibitor, revealing active-site architecture\",\n      \"pmids\": [\"26863983\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Cryo-EM structures of the Pf20S–PfPA28 complex (one and two PA28 caps, resolved at 3.9 Å and 3.8 Å) showed that PA28 binds the 20S core asymmetrically, strongly engaging subunits on only one side; molecular dynamics simulations indicated conformational flexibility at the interface, supporting a lateral-transfer mechanism for release of proteasome degradation products.\",\n      \"method\": \"Cryo-EM single-particle analysis, crystal structure of PfPA28, SAXS, molecular dynamics simulations, genetic deletion of PA28\",\n      \"journal\": \"Nature microbiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — multiple orthogonal structural methods (cryo-EM, crystallography, SAXS) plus MD simulations and genetic validation in a single study\",\n      \"pmids\": [\"31384003\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Cryo-EM structures of Pf20S and human 20S in complex with amino-amide boronate inhibitor MPI-5, and of Pf20S with bortezomib, revealed differences in beta5 active-site binding modes that explain selectivity of these inhibitors for the parasite proteasome over the human enzyme.\",\n      \"method\": \"Cryo-EM structure determination, biochemical inhibition assays, resistance profiling\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — high-resolution cryo-EM structures compared across species with biochemical and cellular validation in a single study\",\n      \"pmids\": [\"34548400\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"High-resolution cryo-EM structures of Pf20S with macrocyclic inhibitor TDI-8304 showed that TDI-8304 binds both the beta2 and beta5 subunits of wild-type Pf20S; a resistance mutation in the beta6 subunit (A117D) eliminates TDI-8304 binding while conferring collateral sensitivity to the beta2 inhibitor WLW-vs, which in the mutant binds both beta2 and beta5.\",\n      \"method\": \"Cryo-EM structure determination, resistance mutation selection, enzymatic and anti-parasite activity assays\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — multiple high-resolution cryo-EM structures (wild-type and mutant Pf20S, human 20S) combined with resistance genetics and functional assays\",\n      \"pmids\": [\"38097652\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Cryo-EM structure of Pf20S in complex with piperidine carboxamide SW584 revealed non-covalent binding in a previously unexplored pocket at the beta5/beta6/beta3 subunit interface (distal from the catalytic threonine); point mutations in the beta5 active site conferred resistance to SW584, confirming beta5 as the primary pharmacological target.\",\n      \"method\": \"Cryo-EM structure determination, resistance selection, biochemical inhibition assays, His8-tag proteasome purification\",\n      \"journal\": \"Cell chemical biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — cryo-EM structure at the subunit interface combined with resistance genetics and biochemical assays in a single study\",\n      \"pmids\": [\"39084225\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_0803800 encodes a beta-type subunit of the P. falciparum 20S proteasome (Pf20S); cryo-EM structures place it within the 20S catalytic core, which assembles with the PA28 regulatory cap asymmetrically and whose beta2, beta5, beta6, and beta3 subunits collectively define species-selective inhibitor-binding pockets that can be exploited for selective antimalarial drug design, while the protein's precise catalytic or structural contribution as the beta-4 subunit specifically has not been individually resolved beyond its membership in the complex.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0803800 encodes a beta-type subunit of the Plasmodium falciparum 20S proteasome (Pf20S), a multi-subunit proteolytic core; the gene was cloned as a 265-amino-acid member of the 20S proteasome beta-subunit family, encoded by a transcript interrupted by a single intron [#0]. Cryo-EM structures of the intact Pf20S place this beta-subunit within the assembled catalytic core alongside the other beta-subunits, and reveal active-site architecture in the core that differs from the human enzyme [#1]. Within the larger complex, Pf20S associates with the PfPA28 regulatory cap, which engages the 20S core asymmetrically and is consistent with a lateral-transfer mechanism for release of degradation products [#2]. The catalytic and inhibitor-binding chemistry of the core has been mapped extensively at the beta2, beta5, beta6, and beta3 subunits, where species-selective pockets are exploited for antimalarial inhibitor design [#3, #4, #5]. Beyond its membership in the Pf20S core established by these structures, the specific catalytic or structural contribution of the PF3D7_0803800 beta-4 subunit as an individual entity has not been resolved in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2000,\n      \"claim\": \"Establishing that P. falciparum possesses this specific proteasome beta-subunit gene defined a candidate component of the parasite's proteolytic machinery at the sequence level.\",\n      \"evidence\": \"Molecular cloning, cDNA/genomic sequence comparison and Northern blot in P. falciparum\",\n      \"pmids\": [\"10856507\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No functional or catalytic assay for the subunit\", \"Assignment within the assembled complex not shown\", \"Whether the subunit is proteolytically active undetermined\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"The first cryo-EM structure of the intact Pf20S positioned the beta-subunits within the catalytic core and exposed parasite-specific active-site features distinguishing it from the human proteasome.\",\n      \"evidence\": \"Cryo-EM single-particle analysis at 3.6 Å of the Pf20S complex in P. falciparum\",\n      \"pmids\": [\"26863983\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Individual catalytic contribution of the beta-4 subunit not isolated\", \"Structure captures the assembled complex, not this subunit in isolation\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Resolving how the PfPA28 regulatory cap docks onto the 20S core clarified the architecture and product-release mechanism of the fuller proteasome assembly containing this subunit.\",\n      \"evidence\": \"Cryo-EM, PfPA28 crystallography, SAXS, molecular dynamics, and PA28 genetic deletion in P. falciparum\",\n      \"pmids\": [\"31384003\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Role of the beta-4 subunit specifically in PA28 engagement not defined\", \"Functional consequence for this subunit not tested\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Comparing Pf20S and human 20S bound to boronate inhibitors explained species selectivity at the beta5 active site, advancing selective antimalarial proteasome inhibitor design.\",\n      \"evidence\": \"Cryo-EM of Pf20S with MPI-5 and bortezomib plus biochemical inhibition and resistance profiling in P. falciparum\",\n      \"pmids\": [\"34548400\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Findings center on beta5, not the beta-4 subunit encoded by PF3D7_0803800\", \"No individual functional role for this subunit\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Mapping dual beta2/beta5 engagement of TDI-8304 and a beta6 resistance mutation defined how inhibitor binding and collateral sensitivity distribute across core beta-subunits.\",\n      \"evidence\": \"Cryo-EM of wild-type and mutant Pf20S with resistance selection and enzymatic/anti-parasite assays in P. falciparum\",\n      \"pmids\": [\"38097652\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Focused on beta2, beta5, beta6, not the beta-4 subunit\", \"No isolated role for PF3D7_0803800\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Identifying a non-covalent inhibitor pocket at the beta5/beta6/beta3 interface expanded the druggable surface of the Pf20S core and confirmed beta5 as the primary pharmacological target.\",\n      \"evidence\": \"Cryo-EM of Pf20S with SW584, resistance selection, and biochemical assays with His8-tag purification in P. falciparum\",\n      \"pmids\": [\"39084225\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"The characterized interface pocket involves beta5/beta6/beta3, not the beta-4 subunit\", \"Contribution of PF3D7_0803800 to this pocket unaddressed\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The individual catalytic or structural role of the PF3D7_0803800 beta-4 subunit, distinct from its membership in the Pf20S core, remains unresolved.\",\n      \"evidence\": \"No timeline discovery isolates the function of this subunit apart from the assembled complex\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No subunit-specific catalytic assay\", \"No inhibitor characterized as binding this subunit specifically\", \"No genetic knockout/knockdown of PF3D7_0803800 alone\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004298\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0043161\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"complexes\": [\n      \"Proteasome 20S core complex (Pf20S)\",\n      \"Pf20S-PfPA28 complex\"\n    ],\n    \"partners\": [\n      \"PfPA28 (proteasome regulatory cap)\"\n    ],\n    \"other_free_text\": [\n      \"Encodes a 265-amino-acid 20S proteasome beta-subunit family member with a single intron [#0]\",\n      \"Positioned within the assembled Pf20S catalytic core by cryo-EM [#1]\",\n      \"Species-selective inhibitor pockets characterized at beta2/beta5/beta6/beta3 subunits of the core, not at the beta-4 subunit specifically [#3, #4, #5]\",\n      \"Individual catalytic/structural role of PF3D7_0803800 as the beta-4 subunit not resolved beyond complex membership\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0803800","name":null,"product":"proteasome subunit beta type-4","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1226500","name":null,"product":"proteasome subunit beta type-4, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0115100","name":null,"product":"proteasome subunit beta type-4, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}