{"gene":"PF3D7_1475600","run_date":"2026-09-08T15:24:04","timeline":{"discoveries":[{"year":2019,"finding":"BDP4 (PF3D7_1475600) was identified as one of 14 putative reader proteins in P. falciparum through histone peptide pull-down experiments, indicating it associates with histone post-translational modification marks; interaction proteomics further placed it within one of five major epigenetic complexes in the parasite.","method":"Histone peptide pull-down (quantitative proteomics) and interaction proteomics (tagging + AP-MS)","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single lab, pull-down plus interaction proteomics are two orthogonal methods, but full complex membership details for BDP4 specifically are not elaborated beyond its identification as a reader protein in the inventory","pmids":["31728527"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2026,"finding":"The bromodomain (BRD) of BDP4 (PF3D7_1475600) is a druggable binding pocket; a stabilized surrogate construct of PfBDP4-BRD enabled experimental validation of virtual-screening hits and determination of a 1.25 Å co-crystal structure with a newly identified small-molecule inhibitor, confirming ligand binding to the bromodomain.","method":"ProteinMPNN-guided sequence design, virtual screening, isothermal titration calorimetry (ITC), X-ray crystallography (co-crystal structure at 1.25 Å)","journal":"Protein science : a publication of the Protein Society","confidence":"High","confidence_rationale":"Tier 1 / Moderate — co-crystal structure at 1.25 Å resolution with experimental ligand validation by ITC-equivalent biophysics, single lab but multiple orthogonal methods (computational design, virtual screening, co-crystallography)","pmids":["42068230"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"BDP4 (PF3D7_1475600) is a bromodomain-containing epigenetic reader protein in P. falciparum that associates with histone post-translational modification marks and participates in one of the parasite's major epigenetic complexes; its bromodomain adopts a defined three-dimensional structure with a ligand-accessible binding pocket, as demonstrated by a 1.25 Å co-crystal structure with a small-molecule inhibitor."},"narrative":{"mechanistic_narrative":"BDP4 (PF3D7_1475600) is a putative bromodomain-containing epigenetic reader protein in Plasmodium falciparum. It was identified through histone peptide pull-down as one of 14 candidate reader proteins that associate with histone post-translational modification marks, and interaction proteomics placed it within one of the parasite's five major epigenetic complexes [PMID:31728527]. Its bromodomain (PfBDP4-BRD) forms a defined, ligand-accessible binding pocket: a stabilized surrogate construct enabled a 1.25 Å co-crystal structure with a small-molecule inhibitor, confirming that the domain is druggable and binds ligand within its pocket [PMID:42068230]. Beyond its identification as a histone-mark-associated reader, its complex membership, and the structural characterization of its bromodomain, no further mechanistic detail — including specific histone marks read, complex partners, or cellular function — has been characterized in the available corpus.","teleology":[{"year":2019,"claim":"Establishing whether PF3D7_1475600 functions as a chromatin reader answered the basic question of its molecular role, placing it among the parasite's histone-mark-recognizing proteins and within an epigenetic complex.","evidence":"Histone peptide pull-down (quantitative proteomics) plus interaction proteomics (tagging + AP-MS) in P. falciparum","pmids":["31728527"],"confidence":"Medium","gaps":["The specific histone post-translational modification mark(s) recognized by BDP4 are not defined","The identity of the co-complex partners for BDP4 specifically is not elaborated","The cellular or developmental function of BDP4 is not established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2026,"claim":"Determining whether the BDP4 bromodomain is a tractable ligand-binding module answered whether the reader domain forms a defined druggable pocket, providing an atomic-resolution structural framework and demonstrating small-molecule engagement.","evidence":"ProteinMPNN-guided surrogate design, virtual screening, ITC, and X-ray co-crystallography at 1.25 Å in P. falciparum","pmids":["42068230"],"confidence":"High","gaps":["The native (non-surrogate) bromodomain structure and its endogenous histone-peptide ligand were not resolved","No cellular consequence of inhibitor binding on BDP4 function was tested","Whether small-molecule occupancy displaces a physiological histone-mark ligand is unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The physiological role of BDP4 — which histone marks it reads, its precise complex composition, and its function in parasite gene regulation or development — remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No genetic loss-of-function or knockdown phenotype for BDP4 is reported in the corpus","No defined endogenous histone-mark specificity","No functional link between bromodomain ligand binding and a downstream parasite process"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Member of one of five major P. falciparum epigenetic complexes (specific complex composition not elaborated) [#0]"],"partners":[],"other_free_text":["Identified as one of 14 putative histone-mark reader proteins in P. falciparum [#0]","Bromodomain (PfBDP4-BRD) forms a ligand-accessible binding pocket resolved by a 1.25 Å co-crystal structure with a small-molecule inhibitor [#1]","Bromodomain is druggable; small-molecule engagement validated by biophysics and co-crystallography [#1]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"31728527","id":"PMC_31728527","title":"Epigenetic reader complexes of the human malaria parasite, Plasmodium falciparum.","date":"2019","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/31728527","citation_count":48,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"42068230","id":"PMC_42068230","title":"Stabilizing Plasmodium falciparum proteins for small molecule drug discovery.","date":"2026","source":"Protein science : a publication of the Protein Society","url":"https://pubmed.ncbi.nlm.nih.gov/42068230","citation_count":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfBDP4"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3801,"output_tokens":707,"usd":0.011004,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5352,"output_tokens":1574,"usd":0.033055,"stage2_stop_reason":"end_turn"},"total_usd":0.044059,"stage1_batch_id":"msgbatch_01S4WrhSkksYHeZXxqf3za3o","stage2_batch_id":"msgbatch_019VBBeuW6G52X8gZfsFDfb5","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2019,\n      \"finding\": \"BDP4 (PF3D7_1475600) was identified as one of 14 putative reader proteins in P. falciparum through histone peptide pull-down experiments, indicating it associates with histone post-translational modification marks; interaction proteomics further placed it within one of five major epigenetic complexes in the parasite.\",\n      \"method\": \"Histone peptide pull-down (quantitative proteomics) and interaction proteomics (tagging + AP-MS)\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single lab, pull-down plus interaction proteomics are two orthogonal methods, but full complex membership details for BDP4 specifically are not elaborated beyond its identification as a reader protein in the inventory\",\n      \"pmids\": [\"31728527\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"The bromodomain (BRD) of BDP4 (PF3D7_1475600) is a druggable binding pocket; a stabilized surrogate construct of PfBDP4-BRD enabled experimental validation of virtual-screening hits and determination of a 1.25 Å co-crystal structure with a newly identified small-molecule inhibitor, confirming ligand binding to the bromodomain.\",\n      \"method\": \"ProteinMPNN-guided sequence design, virtual screening, isothermal titration calorimetry (ITC), X-ray crystallography (co-crystal structure at 1.25 Å)\",\n      \"journal\": \"Protein science : a publication of the Protein Society\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — co-crystal structure at 1.25 Å resolution with experimental ligand validation by ITC-equivalent biophysics, single lab but multiple orthogonal methods (computational design, virtual screening, co-crystallography)\",\n      \"pmids\": [\"42068230\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"BDP4 (PF3D7_1475600) is a bromodomain-containing epigenetic reader protein in P. falciparum that associates with histone post-translational modification marks and participates in one of the parasite's major epigenetic complexes; its bromodomain adopts a defined three-dimensional structure with a ligand-accessible binding pocket, as demonstrated by a 1.25 Å co-crystal structure with a small-molecule inhibitor.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"BDP4 (PF3D7_1475600) is a putative bromodomain-containing epigenetic reader protein in Plasmodium falciparum. It was identified through histone peptide pull-down as one of 14 candidate reader proteins that associate with histone post-translational modification marks, and interaction proteomics placed it within one of the parasite's five major epigenetic complexes [#0]. Its bromodomain (PfBDP4-BRD) forms a defined, ligand-accessible binding pocket: a stabilized surrogate construct enabled a 1.25 Å co-crystal structure with a small-molecule inhibitor, confirming that the domain is druggable and binds ligand within its pocket [#1]. Beyond its identification as a histone-mark-associated reader, its complex membership, and the structural characterization of its bromodomain, no further mechanistic detail — including specific histone marks read, complex partners, or cellular function — has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2019,\n      \"claim\": \"Establishing whether PF3D7_1475600 functions as a chromatin reader answered the basic question of its molecular role, placing it among the parasite's histone-mark-recognizing proteins and within an epigenetic complex.\",\n      \"evidence\": \"Histone peptide pull-down (quantitative proteomics) plus interaction proteomics (tagging + AP-MS) in P. falciparum\",\n      \"pmids\": [\"31728527\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The specific histone post-translational modification mark(s) recognized by BDP4 are not defined\",\n        \"The identity of the co-complex partners for BDP4 specifically is not elaborated\",\n        \"The cellular or developmental function of BDP4 is not established\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Determining whether the BDP4 bromodomain is a tractable ligand-binding module answered whether the reader domain forms a defined druggable pocket, providing an atomic-resolution structural framework and demonstrating small-molecule engagement.\",\n      \"evidence\": \"ProteinMPNN-guided surrogate design, virtual screening, ITC, and X-ray co-crystallography at 1.25 Å in P. falciparum\",\n      \"pmids\": [\"42068230\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The native (non-surrogate) bromodomain structure and its endogenous histone-peptide ligand were not resolved\",\n        \"No cellular consequence of inhibitor binding on BDP4 function was tested\",\n        \"Whether small-molecule occupancy displaces a physiological histone-mark ligand is unknown\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The physiological role of BDP4 — which histone marks it reads, its precise complex composition, and its function in parasite gene regulation or development — remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No genetic loss-of-function or knockdown phenotype for BDP4 is reported in the corpus\",\n        \"No defined endogenous histone-mark specificity\",\n        \"No functional link between bromodomain ligand binding and a downstream parasite process\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140566\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0070491\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [],\n    \"pathway\": [],\n    \"complexes\": [\n      \"Member of one of five major P. falciparum epigenetic complexes (specific complex composition not elaborated) [#0]\"\n    ],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"Identified as one of 14 putative histone-mark reader proteins in P. falciparum [#0]\",\n      \"Bromodomain (PfBDP4-BRD) forms a ligand-accessible binding pocket resolved by a 1.25 Å co-crystal structure with a small-molecule inhibitor [#1]\",\n      \"Bromodomain is druggable; small-molecule engagement validated by biophysics and co-crystallography [#1]\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_1475600","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_0823300, PF3D7_1008100, PF3D7_1014600). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1475600","name":null,"product":"bromodomain protein 4, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1300600","name":null,"product":"bromodomain protein 4, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1245900","name":null,"product":"bromodomain protein 4, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"BDP4","evaluation":null}