{"gene":"TG_202540","gene_symbol":"PDE1","run_date":"2026-09-07T10:25:42","timeline":{"discoveries":[{"year":2022,"finding":"TgPDE1 hydrolyzes both cGMP and cAMP (dual-substrate phosphodiesterase activity), as demonstrated by biochemical analysis of TgPDE1 purified from Toxoplasma lysates.","method":"Biochemical enzyme activity assay on protein purified from Toxoplasma lysates","journal":"mSphere","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro enzymatic activity assay replicated across two independent labs (PMID:35107337 and PMID:36382189) with concordant results","pmids":["35107337","36382189"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"finding":"TgPDE1 is preferentially primed to hydrolyze cGMP with a Km of 18 µM, consistent with dual-substrate activity but cGMP preference.","method":"In vitro enzyme kinetics (Km determination)","journal":"Computational and structural biotechnology journal","confidence":"High","confidence_rationale":"Tier 1 / Moderate — direct in vitro kinetic measurement, single lab but rigorous quantitative assay","pmids":["36382189"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"finding":"TgPDE1 knockdown causes severe growth defects specifically linked to defects in extracellular motility, establishing TgPDE1 as a regulator of tachyzoite motility.","method":"Knockdown screen followed by motility and lytic growth assays","journal":"mSphere","confidence":"High","confidence_rationale":"Tier 2 / Strong — loss-of-function with defined cellular phenotype, replicated in two independent studies (PMID:35107337 and PMID:36382189)","pmids":["35107337","36382189"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"finding":"TgPDE1 localizes to the plasma membrane and cytomembranous compartments in tachyzoites; immuno-electron microscopy further resolved localization to the inner membrane complex, apical pole, plasma membrane, cytosol, dense granules, and rhoptries.","method":"Fluorescence localization (plasma membrane/cytomembranous) and immuno-electron microscopy","journal":"mSphere / Computational and structural biotechnology journal","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct localization by two orthogonal methods (fluorescence and immuno-EM) across two independent labs","pmids":["35107337","36382189"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"finding":"TgPDE1 interactome studies indicate it does not physically interact with TgPDE2 or other TgPDEs, but may be regulated by kinases and proteases; a retinue of interacting kinases and phosphatases was identified.","method":"Interactome/co-immunoprecipitation and mass spectrometry","journal":"mSphere / Computational and structural biotechnology journal","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — interactome data from two labs, but only partial mechanistic follow-up on identified interactors","pmids":["35107337","36382189"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"finding":"Combined loss of TgPDE1 and TgPDE2 is lethal to the parasite, establishing that these two enzymes are collectively essential for tachyzoite viability and that their functions are non-redundant.","method":"Double mutant genetic analysis with lethality readout","journal":"Computational and structural biotechnology journal","confidence":"High","confidence_rationale":"Tier 2 / Moderate — genetic epistasis (double mutant lethality) with clear phenotypic readout, single lab but rigorous genetic approach","pmids":["36382189"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"finding":"TgPDE1 is a target of the PDE inhibitors BIPPO and zaprinast, as demonstrated by enzyme inhibition assays combined with chemogenetic phenotyping.","method":"Enzyme inhibition assays and chemogenetic phenotyping","journal":"Computational and structural biotechnology journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — two orthogonal methods (biochemical inhibition + chemogenetics) in a single lab","pmids":["36382189"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"finding":"TgPDE1 is required for optimal parasite proliferation, gliding motility, invasion, and egress of tachyzoites, as revealed by in vitro phenotyping of TgPDE1 mutants.","method":"In vitro phenotyping of conditional mutants (proliferation, motility, invasion, egress assays)","journal":"Computational and structural biotechnology journal","confidence":"High","confidence_rationale":"Tier 2 / Strong — loss-of-function with multiple defined cellular phenotypes, confirmed across two independent studies","pmids":["36382189","35107337"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2020,"finding":"TgPDE1 is expressed during the tachyzoite lytic cycle in human cells, as confirmed by genomic epitope-tagging.","method":"Genomic epitope-tagging and expression detection","journal":"Computational and structural biotechnology journal","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct epitope-tag expression confirmed across two labs","pmids":["33335684"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"TgPDE1 is a dual-substrate (cGMP-preferred, Km 18 µM; also cAMP) phosphodiesterase that localizes to the plasma membrane, inner membrane complex, apical pole, dense granules, and rhoptries, and is individually required for tachyzoite gliding motility, proliferation, invasion, and egress, while collective loss of TgPDE1 and TgPDE2 is lethal; its activity is inhibited by BIPPO and zaprinast, and it is likely regulated by associated kinases and phosphatases."},"narrative":{"mechanistic_narrative":"TgPDE1 is a cyclic-nucleotide phosphodiesterase that regulates cyclic-nucleotide signaling underlying the motile behaviors of the Toxoplasma gondii tachyzoite [PMID:35107337, PMID:36382189]. It is a dual-substrate enzyme that hydrolyzes both cGMP and cAMP, with a kinetic preference for cGMP (Km 18 µM) [PMID:35107337, PMID:36382189], and its catalytic activity is blocked by the PDE inhibitors BIPPO and zaprinast [PMID:36382189]. The enzyme distributes across the plasma membrane, inner membrane complex, apical pole, cytosol, dense granules, and rhoptries [PMID:35107337, PMID:36382189], consistent with its role in coordinating the surface and secretory events of the lytic cycle. Functionally, TgPDE1 is required for optimal tachyzoite proliferation, gliding motility, invasion, and egress [PMID:35107337, PMID:36382189], and although it does not physically associate with TgPDE2, the two enzymes are collectively essential and non-redundant, since their combined loss is lethal [PMID:35107337, PMID:36382189]. Interactome analysis identified associated kinases and phosphatases that may regulate the enzyme [PMID:35107337, PMID:36382189]; the precise regulatory mechanism has not been resolved in the available corpus.","teleology":[{"year":2020,"claim":"Establishing that TgPDE1 is actually expressed during the disease-relevant tachyzoite stage was the prerequisite for assigning it any role in the lytic cycle.","evidence":"Genomic epitope-tagging and expression detection during the tachyzoite lytic cycle","pmids":["33335684"],"confidence":"Medium","gaps":["Does not address enzymatic activity, substrate, or function","Expression level and stage-specificity not quantified"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"claim":"Biochemical characterization answered what TgPDE1 does enzymatically, showing it hydrolyzes both cyclic nucleotides but is kinetically tuned to cGMP.","evidence":"In vitro enzyme activity assays and Km determination on protein purified from Toxoplasma lysates","pmids":["35107337","36382189"],"confidence":"High","gaps":["Relative in vivo flux through cGMP vs cAMP not determined","No structural basis for substrate preference"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"claim":"Loss-of-function phenotyping connected TgPDE1 activity to specific cellular processes, defining it as a regulator of motility, invasion, egress, and proliferation.","evidence":"Knockdown/conditional mutant phenotyping with motility, invasion, egress, and lytic growth assays","pmids":["35107337","36382189"],"confidence":"High","gaps":["Which cyclic-nucleotide pool drives each phenotype is not resolved","Downstream effectors (e.g. PKG/PKA) not directly linked"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"claim":"Localization studies placed TgPDE1 at the surface and secretory compartments, spatially rationalizing its role in gliding and invasion.","evidence":"Fluorescence microscopy and immuno-electron microscopy in tachyzoites","pmids":["35107337","36382189"],"confidence":"High","gaps":["Functional significance of each subcellular pool not dissected","Membrane-association determinants unknown"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"claim":"Genetic epistasis established that TgPDE1 and TgPDE2 are collectively essential and non-redundant, defining the essentiality logic of the PDE repertoire.","evidence":"Double-mutant genetic analysis with lethality readout, plus interactome showing no physical PDE-PDE interaction","pmids":["36382189","35107337"],"confidence":"High","gaps":["Molecular basis of non-redundancy (distinct pools vs distinct substrates) unresolved","No reciprocal validation of interactome kinases/phosphatases as functional regulators"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"claim":"Chemogenetic and inhibition assays identified TgPDE1 as a target of BIPPO and zaprinast, providing a pharmacological handle on its activity.","evidence":"Enzyme inhibition assays combined with chemogenetic phenotyping","pmids":["36382189"],"confidence":"Medium","gaps":["Inhibitor selectivity across TgPDEs not fully defined","In vivo consequences of inhibition on parasite viability not quantified"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"How TgPDE1 activity is regulated by its associated kinases and phosphatases, and how its distinct subcellular pools contribute to motility, invasion, and egress, remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No functional validation of identified kinase/phosphatase regulators","No structural model of the catalytic or regulatory domains","Contribution of individual subcellular pools not separated"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":["Does not physically interact with TgPDE2 or other TgPDEs, yet the two enzymes are collectively essential and non-redundant [#4, #5].","Interactome identified associated kinases and phosphatases as candidate regulators [#4]."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"35107337","id":"PMC_35107337","title":"Functional Analysis of the Expanded Phosphodiesterase Gene Family in Toxoplasma gondii Tachyzoites.","date":"2022","source":"mSphere","url":"https://pubmed.ncbi.nlm.nih.gov/35107337","citation_count":19,"is_preprint":false},{"pmid":"33335684","id":"PMC_33335684","title":"The protozoan parasite Toxoplasma gondii encodes a gamut of phosphodiesterases during its lytic cycle in human cells.","date":"2020","source":"Computational and structural biotechnology journal","url":"https://pubmed.ncbi.nlm.nih.gov/33335684","citation_count":9,"is_preprint":false},{"pmid":"36382189","id":"PMC_36382189","title":"Plasticity and therapeutic potential of cAMP and cGMP-specific phosphodiesterases in Toxoplasma gondii.","date":"2022","source":"Computational and structural biotechnology journal","url":"https://pubmed.ncbi.nlm.nih.gov/36382189","citation_count":6,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4338,"output_tokens":1987,"usd":0.02141,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7362,"output_tokens":2824,"usd":0.053705,"stage2_stop_reason":"end_turn"},"total_usd":0.075115,"stage1_batch_id":"msgbatch_018xTxyBPcQFK9jdgubtxgsj","stage2_batch_id":"msgbatch_01UiG5BTaJP7BvKKL6RLeyv2","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2022,\n      \"finding\": \"TgPDE1 hydrolyzes both cGMP and cAMP (dual-substrate phosphodiesterase activity), as demonstrated by biochemical analysis of TgPDE1 purified from Toxoplasma lysates.\",\n      \"method\": \"Biochemical enzyme activity assay on protein purified from Toxoplasma lysates\",\n      \"journal\": \"mSphere\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro enzymatic activity assay replicated across two independent labs (PMID:35107337 and PMID:36382189) with concordant results\",\n      \"pmids\": [\"35107337\", \"36382189\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"TgPDE1 is preferentially primed to hydrolyze cGMP with a Km of 18 µM, consistent with dual-substrate activity but cGMP preference.\",\n      \"method\": \"In vitro enzyme kinetics (Km determination)\",\n      \"journal\": \"Computational and structural biotechnology journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — direct in vitro kinetic measurement, single lab but rigorous quantitative assay\",\n      \"pmids\": [\"36382189\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"TgPDE1 knockdown causes severe growth defects specifically linked to defects in extracellular motility, establishing TgPDE1 as a regulator of tachyzoite motility.\",\n      \"method\": \"Knockdown screen followed by motility and lytic growth assays\",\n      \"journal\": \"mSphere\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — loss-of-function with defined cellular phenotype, replicated in two independent studies (PMID:35107337 and PMID:36382189)\",\n      \"pmids\": [\"35107337\", \"36382189\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"TgPDE1 localizes to the plasma membrane and cytomembranous compartments in tachyzoites; immuno-electron microscopy further resolved localization to the inner membrane complex, apical pole, plasma membrane, cytosol, dense granules, and rhoptries.\",\n      \"method\": \"Fluorescence localization (plasma membrane/cytomembranous) and immuno-electron microscopy\",\n      \"journal\": \"mSphere / Computational and structural biotechnology journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct localization by two orthogonal methods (fluorescence and immuno-EM) across two independent labs\",\n      \"pmids\": [\"35107337\", \"36382189\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"TgPDE1 interactome studies indicate it does not physically interact with TgPDE2 or other TgPDEs, but may be regulated by kinases and proteases; a retinue of interacting kinases and phosphatases was identified.\",\n      \"method\": \"Interactome/co-immunoprecipitation and mass spectrometry\",\n      \"journal\": \"mSphere / Computational and structural biotechnology journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — interactome data from two labs, but only partial mechanistic follow-up on identified interactors\",\n      \"pmids\": [\"35107337\", \"36382189\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Combined loss of TgPDE1 and TgPDE2 is lethal to the parasite, establishing that these two enzymes are collectively essential for tachyzoite viability and that their functions are non-redundant.\",\n      \"method\": \"Double mutant genetic analysis with lethality readout\",\n      \"journal\": \"Computational and structural biotechnology journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis (double mutant lethality) with clear phenotypic readout, single lab but rigorous genetic approach\",\n      \"pmids\": [\"36382189\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"TgPDE1 is a target of the PDE inhibitors BIPPO and zaprinast, as demonstrated by enzyme inhibition assays combined with chemogenetic phenotyping.\",\n      \"method\": \"Enzyme inhibition assays and chemogenetic phenotyping\",\n      \"journal\": \"Computational and structural biotechnology journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — two orthogonal methods (biochemical inhibition + chemogenetics) in a single lab\",\n      \"pmids\": [\"36382189\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"TgPDE1 is required for optimal parasite proliferation, gliding motility, invasion, and egress of tachyzoites, as revealed by in vitro phenotyping of TgPDE1 mutants.\",\n      \"method\": \"In vitro phenotyping of conditional mutants (proliferation, motility, invasion, egress assays)\",\n      \"journal\": \"Computational and structural biotechnology journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — loss-of-function with multiple defined cellular phenotypes, confirmed across two independent studies\",\n      \"pmids\": [\"36382189\", \"35107337\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"TgPDE1 is expressed during the tachyzoite lytic cycle in human cells, as confirmed by genomic epitope-tagging.\",\n      \"method\": \"Genomic epitope-tagging and expression detection\",\n      \"journal\": \"Computational and structural biotechnology journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct epitope-tag expression confirmed across two labs\",\n      \"pmids\": [\"33335684\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"TgPDE1 is a dual-substrate (cGMP-preferred, Km 18 µM; also cAMP) phosphodiesterase that localizes to the plasma membrane, inner membrane complex, apical pole, dense granules, and rhoptries, and is individually required for tachyzoite gliding motility, proliferation, invasion, and egress, while collective loss of TgPDE1 and TgPDE2 is lethal; its activity is inhibited by BIPPO and zaprinast, and it is likely regulated by associated kinases and phosphatases.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TgPDE1 is a cyclic-nucleotide phosphodiesterase that regulates cyclic-nucleotide signaling underlying the motile behaviors of the Toxoplasma gondii tachyzoite [#0, #7]. It is a dual-substrate enzyme that hydrolyzes both cGMP and cAMP, with a kinetic preference for cGMP (Km 18 µM) [#0, #1], and its catalytic activity is blocked by the PDE inhibitors BIPPO and zaprinast [#6]. The enzyme distributes across the plasma membrane, inner membrane complex, apical pole, cytosol, dense granules, and rhoptries [#3], consistent with its role in coordinating the surface and secretory events of the lytic cycle. Functionally, TgPDE1 is required for optimal tachyzoite proliferation, gliding motility, invasion, and egress [#2, #7], and although it does not physically associate with TgPDE2, the two enzymes are collectively essential and non-redundant, since their combined loss is lethal [#4, #5]. Interactome analysis identified associated kinases and phosphatases that may regulate the enzyme [#4]; the precise regulatory mechanism has not been resolved in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2020,\n      \"claim\": \"Establishing that TgPDE1 is actually expressed during the disease-relevant tachyzoite stage was the prerequisite for assigning it any role in the lytic cycle.\",\n      \"evidence\": \"Genomic epitope-tagging and expression detection during the tachyzoite lytic cycle\",\n      \"pmids\": [\"33335684\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Does not address enzymatic activity, substrate, or function\", \"Expression level and stage-specificity not quantified\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Biochemical characterization answered what TgPDE1 does enzymatically, showing it hydrolyzes both cyclic nucleotides but is kinetically tuned to cGMP.\",\n      \"evidence\": \"In vitro enzyme activity assays and Km determination on protein purified from Toxoplasma lysates\",\n      \"pmids\": [\"35107337\", \"36382189\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Relative in vivo flux through cGMP vs cAMP not determined\", \"No structural basis for substrate preference\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Loss-of-function phenotyping connected TgPDE1 activity to specific cellular processes, defining it as a regulator of motility, invasion, egress, and proliferation.\",\n      \"evidence\": \"Knockdown/conditional mutant phenotyping with motility, invasion, egress, and lytic growth assays\",\n      \"pmids\": [\"35107337\", \"36382189\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Which cyclic-nucleotide pool drives each phenotype is not resolved\", \"Downstream effectors (e.g. PKG/PKA) not directly linked\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Localization studies placed TgPDE1 at the surface and secretory compartments, spatially rationalizing its role in gliding and invasion.\",\n      \"evidence\": \"Fluorescence microscopy and immuno-electron microscopy in tachyzoites\",\n      \"pmids\": [\"35107337\", \"36382189\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional significance of each subcellular pool not dissected\", \"Membrane-association determinants unknown\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Genetic epistasis established that TgPDE1 and TgPDE2 are collectively essential and non-redundant, defining the essentiality logic of the PDE repertoire.\",\n      \"evidence\": \"Double-mutant genetic analysis with lethality readout, plus interactome showing no physical PDE-PDE interaction\",\n      \"pmids\": [\"36382189\", \"35107337\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular basis of non-redundancy (distinct pools vs distinct substrates) unresolved\", \"No reciprocal validation of interactome kinases/phosphatases as functional regulators\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Chemogenetic and inhibition assays identified TgPDE1 as a target of BIPPO and zaprinast, providing a pharmacological handle on its activity.\",\n      \"evidence\": \"Enzyme inhibition assays combined with chemogenetic phenotyping\",\n      \"pmids\": [\"36382189\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Inhibitor selectivity across TgPDEs not fully defined\", \"In vivo consequences of inhibition on parasite viability not quantified\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How TgPDE1 activity is regulated by its associated kinases and phosphatases, and how its distinct subcellular pools contribute to motility, invasion, and egress, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No functional validation of identified kinase/phosphatase regulators\", \"No structural model of the catalytic or regulatory domains\", \"Contribution of individual subcellular pools not separated\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004114\", \"supporting_discovery_ids\": [0, 1, 6], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0004115\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0047555\", \"supporting_discovery_ids\": [0, 1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [3], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0070258\", \"supporting_discovery_ids\": [3], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0031410\", \"supporting_discovery_ids\": [3], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0020003\", \"supporting_discovery_ids\": [3], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0019935\", \"supporting_discovery_ids\": [0, 2, 7], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0071902\", \"supporting_discovery_ids\": [2, 7], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"Does not physically interact with TgPDE2 or other TgPDEs, yet the two enzymes are collectively essential and non-redundant [#4, #5].\",\n      \"Interactome identified associated kinases and phosphatases as candidate regulators [#4].\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_202540","name":"PDE1","product":"3'5'-cyclic nucleotide phosphodiesterase PDE1","uniprot_acc":"S8F656","chromosome":"TGME49_chrVIIa","start_pos":3235830},{"strain":"GT1","gene_id":"TGGT1_202540","name":null,"product":"3'5'-cyclic nucleotide phosphodiesterase domain-containing protein","uniprot_acc":null,"chromosome":"TGGT1_chrVIIa","start_pos":3136489},{"strain":"RH88","gene_id":"TGRH88_036470","name":null,"product":"3'5'-cyclic nucleotide phosphodiesterase domain-containing protein","uniprot_acc":null,"chromosome":"CM023088","start_pos":3331392},{"strain":"VEG","gene_id":"TGVEG_202540","name":null,"product":"3'5'-cyclic nucleotide phosphodiesterase domain-containing protein","uniprot_acc":"B9QFV9","chromosome":"TGVEG_chrVIIa","start_pos":3325743}]}