{"gene":"PF3D7_0809700","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2012,"finding":"PfRuvB1 (PF3D7_0809700) is an active ATPase whose activity is significantly stimulated by single-stranded DNA, and it also possesses DNA helicase activity that translocates preferentially in the 5′-to-3′ direction, as determined by biochemical characterization of the recombinant protein.","method":"In vitro ATPase assay with recombinant protein (stimulation by ssDNA measured), DNA helicase/unwinding assay establishing 5′→3′ directionality","journal":"Gene","confidence":"High","confidence_rationale":"Tier 1 / Moderate — direct in vitro enzymatic assays (ATPase + helicase) with recombinant protein, two orthogonal biochemical methods in a single focused study","pmids":["23219504"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2012,"finding":"PfRuvB1 (PF3D7_0809700) is constitutively expressed during all stages of the intraerythrocytic cycle and localizes predominantly to the nucleus, as shown by in vivo stage-specific expression analysis and subcellular localization.","method":"Stage-specific expression analysis and subcellular localization (in vivo investigation during intraerythrocytic cycle)","journal":"Gene","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — localization result from a single lab study; method details (e.g. immunofluorescence) not fully specified in abstract","pmids":["23219504"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"finding":"PfRuvB1 (PF3D7_0809700) does NOT interact with PfRuvB2 in vitro; PfRuvB2 interacts only with PfRuvB3 but not with PfRuvB1, establishing that PfRuvB1 is excluded from the PfRuvB2/PfRuvB3 complex.","method":"In vitro interaction (pulldown/binding) assay between recombinant RuvB proteins","journal":"Biochimica et biophysica acta","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct in vitro interaction assay from single lab; result is a confirmed negative interaction relevant to PF3D7_0809700 complex membership","pmids":["24161468"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"finding":"Novobiocin inhibits PfRuvB1 (PF3D7_0809700) ATPase activity considerably and its helicase activity potently, likely by competing with ATP binding at the active site; cisplatin and ciprofloxacin partially inhibit ATPase activity; actinomycin and ethidium bromide are potent helicase inhibitors.","method":"In vitro ATPase inhibition assay and helicase inhibition assay with recombinant PfRuvB1 in the presence of various chemical compounds","journal":"Protoplasma","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in vitro enzymatic assays with defined inhibitors, but single lab and no mutagenesis to confirm binding site","pmids":["24934654"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_0809700 (RUVB1) encodes an AAA+ ATPase/DNA helicase that unwinds DNA with 5′-to-3′ directionality; its ATPase activity is stimulated by ssDNA; it is constitutively expressed throughout the intraerythrocytic cycle and localizes to the nucleus; it does not interact with PfRuvB2, distinguishing it from the PfRuvB2/PfRuvB3 complex; and its enzymatic activities can be inhibited in vitro by novobiocin (via competition at the ATP-binding site), actinomycin, and ethidium bromide."},"narrative":{"mechanistic_narrative":"PF3D7_0809700 (RUVB1) encodes a nucleic-acid-stimulated AAA+ ATPase and DNA helicase of Plasmodium falciparum [PMID:23219504]. Recombinant PfRuvB1 hydrolyzes ATP in a reaction significantly stimulated by single-stranded DNA and unwinds DNA with a preferential 5′-to-3′ translocation polarity [PMID:23219504]. The protein is constitutively expressed across all stages of the intraerythrocytic cycle and localizes predominantly to the nucleus, consistent with a role acting on DNA substrates [PMID:23219504]. Despite being a RuvB-family member, PfRuvB1 does not interact with PfRuvB2 in vitro—PfRuvB2 associates only with PfRuvB3—placing PfRuvB1 outside the PfRuvB2/PfRuvB3 complex and indicating it functions in a distinct assembly or context [PMID:24161468]. Its enzymatic activities are pharmacologically tractable: novobiocin considerably inhibits its ATPase and potently inhibits its helicase activity, likely by competing at the ATP-binding site, while actinomycin and ethidium bromide are potent helicase inhibitors [PMID:24934654]. Beyond these in vitro biochemical and localization findings, the cellular pathway and physiological substrates of PF3D7_0809700 have not been characterized in the available corpus.","teleology":[{"year":2012,"claim":"Establishing whether the RuvB1 gene product is an active enzyme, biochemical characterization showed it is a bona fide ssDNA-stimulated ATPase and a directional DNA helicase, defining its core molecular activity.","evidence":"In vitro ATPase assay and DNA unwinding assay with recombinant protein, establishing ssDNA stimulation and 5′→3′ directionality","pmids":["23219504"],"confidence":"High","gaps":["Physiological DNA substrate not identified","No structural or mutagenesis data mapping the ATP/DNA-binding residues","Cellular pathway in which the helicase acts unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2012,"claim":"Determining when and where the enzyme operates, expression and localization analysis showed it is constitutively present throughout the intraerythrocytic cycle and nuclear, consistent with a DNA-acting role.","evidence":"Stage-specific expression analysis and subcellular localization during the intraerythrocytic cycle","pmids":["23219504"],"confidence":"Medium","gaps":["Method details of localization not fully specified","No functional link between nuclear localization and a specific DNA transaction"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"claim":"Addressing whether PfRuvB1 partners with the other Plasmodium RuvB proteins, interaction assays showed it does not bind PfRuvB2 (which associates only with PfRuvB3), excluding PfRuvB1 from the PfRuvB2/PfRuvB3 complex.","evidence":"In vitro pulldown/binding assays between recombinant Plasmodium RuvB proteins","pmids":["24161468"],"confidence":"Medium","gaps":["The actual protein partners or complex of PfRuvB1 remain unidentified","Negative interaction shown in vitro only, not in cellular context"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"claim":"Probing pharmacological tractability, inhibition assays showed novobiocin blocks ATPase and helicase activity (likely via ATP-site competition) and identified actinomycin and ethidium bromide as potent helicase inhibitors, defining druggable enzymatic activities.","evidence":"In vitro ATPase and helicase inhibition assays with recombinant PfRuvB1 and defined chemical compounds","pmids":["24934654"],"confidence":"Medium","gaps":["ATP-site competition mechanism inferred, not confirmed by mutagenesis or structure","No demonstration that inhibition translates to parasite killing"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The in vivo function, physiological substrates, protein partners, and the cellular DNA transaction served by PF3D7_0809700 remain undefined.","evidence":"","pmids":[],"confidence":"Low","gaps":["No identification of the complex or partners PfRuvB1 does belong to","No genetic/knockdown evidence for its cellular role","No structural model"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":["Does NOT interact with PfRuvB2; PfRuvB2 binds only PfRuvB3, excluding PF3D7_0809700 from the PfRuvB2/PfRuvB3 complex [#2]","Constitutively expressed across all intraerythrocytic stages [#1]","Enzymatic activities inhibited in vitro by novobiocin (likely ATP-site competition), and helicase potently inhibited by actinomycin and ethidium bromide [#3]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"23219504","id":"PMC_23219504","title":"Plasmodium falciparum RuvB1 is an active DNA helicase and translocates in the 5'-3' direction.","date":"2012","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/23219504","citation_count":14,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RUVB1","PfRUVB1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"24161468","id":"PMC_24161468","title":"Plasmodium falciparum RuvB2 translocates in 5'-3' direction, relocalizes during schizont stage and its enzymatic activities are up regulated by RuvB3 of the same complex.","date":"2013","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/24161468","citation_count":12,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RUVB1","PfRUVB1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"24934654","id":"PMC_24934654","title":"Identification of inhibitors of Plasmodium falciparum RuvB1 helicase using biochemical assays.","date":"2014","source":"Protoplasma","url":"https://pubmed.ncbi.nlm.nih.gov/24934654","citation_count":6,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RUVB1","PfRUVB1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4381,"output_tokens":1199,"usd":0.015564,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6025,"output_tokens":2218,"usd":0.042787,"stage2_stop_reason":"end_turn"},"total_usd":0.058351,"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\": 2012,\n      \"finding\": \"PfRuvB1 (PF3D7_0809700) is an active ATPase whose activity is significantly stimulated by single-stranded DNA, and it also possesses DNA helicase activity that translocates preferentially in the 5′-to-3′ direction, as determined by biochemical characterization of the recombinant protein.\",\n      \"method\": \"In vitro ATPase assay with recombinant protein (stimulation by ssDNA measured), DNA helicase/unwinding assay establishing 5′→3′ directionality\",\n      \"journal\": \"Gene\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — direct in vitro enzymatic assays (ATPase + helicase) with recombinant protein, two orthogonal biochemical methods in a single focused study\",\n      \"pmids\": [\"23219504\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"PfRuvB1 (PF3D7_0809700) is constitutively expressed during all stages of the intraerythrocytic cycle and localizes predominantly to the nucleus, as shown by in vivo stage-specific expression analysis and subcellular localization.\",\n      \"method\": \"Stage-specific expression analysis and subcellular localization (in vivo investigation during intraerythrocytic cycle)\",\n      \"journal\": \"Gene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — localization result from a single lab study; method details (e.g. immunofluorescence) not fully specified in abstract\",\n      \"pmids\": [\"23219504\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"PfRuvB1 (PF3D7_0809700) does NOT interact with PfRuvB2 in vitro; PfRuvB2 interacts only with PfRuvB3 but not with PfRuvB1, establishing that PfRuvB1 is excluded from the PfRuvB2/PfRuvB3 complex.\",\n      \"method\": \"In vitro interaction (pulldown/binding) assay between recombinant RuvB proteins\",\n      \"journal\": \"Biochimica et biophysica acta\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct in vitro interaction assay from single lab; result is a confirmed negative interaction relevant to PF3D7_0809700 complex membership\",\n      \"pmids\": [\"24161468\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Novobiocin inhibits PfRuvB1 (PF3D7_0809700) ATPase activity considerably and its helicase activity potently, likely by competing with ATP binding at the active site; cisplatin and ciprofloxacin partially inhibit ATPase activity; actinomycin and ethidium bromide are potent helicase inhibitors.\",\n      \"method\": \"In vitro ATPase inhibition assay and helicase inhibition assay with recombinant PfRuvB1 in the presence of various chemical compounds\",\n      \"journal\": \"Protoplasma\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro enzymatic assays with defined inhibitors, but single lab and no mutagenesis to confirm binding site\",\n      \"pmids\": [\"24934654\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_0809700 (RUVB1) encodes an AAA+ ATPase/DNA helicase that unwinds DNA with 5′-to-3′ directionality; its ATPase activity is stimulated by ssDNA; it is constitutively expressed throughout the intraerythrocytic cycle and localizes to the nucleus; it does not interact with PfRuvB2, distinguishing it from the PfRuvB2/PfRuvB3 complex; and its enzymatic activities can be inhibited in vitro by novobiocin (via competition at the ATP-binding site), actinomycin, and ethidium bromide.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0809700 (RUVB1) encodes a nucleic-acid-stimulated AAA+ ATPase and DNA helicase of Plasmodium falciparum [#0]. Recombinant PfRuvB1 hydrolyzes ATP in a reaction significantly stimulated by single-stranded DNA and unwinds DNA with a preferential 5′-to-3′ translocation polarity [#0]. The protein is constitutively expressed across all stages of the intraerythrocytic cycle and localizes predominantly to the nucleus, consistent with a role acting on DNA substrates [#1]. Despite being a RuvB-family member, PfRuvB1 does not interact with PfRuvB2 in vitro—PfRuvB2 associates only with PfRuvB3—placing PfRuvB1 outside the PfRuvB2/PfRuvB3 complex and indicating it functions in a distinct assembly or context [#2]. Its enzymatic activities are pharmacologically tractable: novobiocin considerably inhibits its ATPase and potently inhibits its helicase activity, likely by competing at the ATP-binding site, while actinomycin and ethidium bromide are potent helicase inhibitors [#3]. Beyond these in vitro biochemical and localization findings, the cellular pathway and physiological substrates of PF3D7_0809700 have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2012,\n      \"claim\": \"Establishing whether the RuvB1 gene product is an active enzyme, biochemical characterization showed it is a bona fide ssDNA-stimulated ATPase and a directional DNA helicase, defining its core molecular activity.\",\n      \"evidence\": \"In vitro ATPase assay and DNA unwinding assay with recombinant protein, establishing ssDNA stimulation and 5′→3′ directionality\",\n      \"pmids\": [\"23219504\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Physiological DNA substrate not identified\",\n        \"No structural or mutagenesis data mapping the ATP/DNA-binding residues\",\n        \"Cellular pathway in which the helicase acts unknown\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Determining when and where the enzyme operates, expression and localization analysis showed it is constitutively present throughout the intraerythrocytic cycle and nuclear, consistent with a DNA-acting role.\",\n      \"evidence\": \"Stage-specific expression analysis and subcellular localization during the intraerythrocytic cycle\",\n      \"pmids\": [\"23219504\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Method details of localization not fully specified\",\n        \"No functional link between nuclear localization and a specific DNA transaction\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Addressing whether PfRuvB1 partners with the other Plasmodium RuvB proteins, interaction assays showed it does not bind PfRuvB2 (which associates only with PfRuvB3), excluding PfRuvB1 from the PfRuvB2/PfRuvB3 complex.\",\n      \"evidence\": \"In vitro pulldown/binding assays between recombinant Plasmodium RuvB proteins\",\n      \"pmids\": [\"24161468\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The actual protein partners or complex of PfRuvB1 remain unidentified\",\n        \"Negative interaction shown in vitro only, not in cellular context\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Probing pharmacological tractability, inhibition assays showed novobiocin blocks ATPase and helicase activity (likely via ATP-site competition) and identified actinomycin and ethidium bromide as potent helicase inhibitors, defining druggable enzymatic activities.\",\n      \"evidence\": \"In vitro ATPase and helicase inhibition assays with recombinant PfRuvB1 and defined chemical compounds\",\n      \"pmids\": [\"24934654\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"ATP-site competition mechanism inferred, not confirmed by mutagenesis or structure\",\n        \"No demonstration that inhibition translates to parasite killing\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The in vivo function, physiological substrates, protein partners, and the cellular DNA transaction served by PF3D7_0809700 remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No identification of the complex or partners PfRuvB1 does belong to\",\n        \"No genetic/knockdown evidence for its cellular role\",\n        \"No structural model\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0043139\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0016887\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0003678\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0043142\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"Does NOT interact with PfRuvB2; PfRuvB2 binds only PfRuvB3, excluding PF3D7_0809700 from the PfRuvB2/PfRuvB3 complex [#2]\",\n      \"Constitutively expressed across all intraerythrocytic stages [#1]\",\n      \"Enzymatic activities inhibited in vitro by novobiocin (likely ATP-site competition), and helicase potently inhibited by actinomycin and ethidium bromide [#3]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0809700","name":null,"product":"RuvB-like helicase 1","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1427700","name":null,"product":"RuvB-like helicase 1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1431000","name":null,"product":"RuvB-like helicase 1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"RUVB1","evaluation":null}