{"gene":"PF3D7_1121900","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2021,"finding":"PfPDK1 (PF3D7_1121900) is required to activate the catalytic subunit of protein kinase A (PfPKAc) in P. falciparum blood-stage parasites. Whole-genome sequencing of parasite mutants selected to tolerate lethal PfPKAc overexpression identified missense mutations exclusively in the gene encoding PfPDK1. Targeted mutagenesis confirmed that PfPDK1 activates PfPKAc, and that threonine 189 (T189) in the PfPKAc activation loop is the critical target residue phosphorylated by PfPDK1.","method":"Whole-genome sequencing of suppressor mutants + targeted mutagenesis (activation-loop phosphorylation) + conditional knockdown","journal":"PLoS biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (WGS suppressor screen, targeted mutagenesis of activation-loop residue, conditional knockdown) in a single rigorous study establishing the PDK1→PKAc T189 phosphorylation axis","pmids":["34879056"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"finding":"Conditional knockdown of PfPDK1 demonstrated that PfPDK1 is involved in regulating gametocyte deformability in P. falciparum, establishing a functional role for PfPDK1 in the sexual blood-stage forms.","method":"Conditional knockdown (cKD) with phenotypic readout of gametocyte deformability","journal":"PLoS biology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — single lab, single conditional knockdown experiment with a defined cellular phenotype but no downstream molecular mechanism identified for this specific phenotype","pmids":["34879056"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"finding":"In a drug-resistance selection experiment with a PDEβ inhibitor (5-benzyl compound SAL-0010003), whole-genome sequencing of resistant parasites detected a missense mutation in PfPDK1 (PF3D7_1121900): an asparagine-to-isoleucine substitution at position 324, immediately downstream of the activation loop. This finding independently corroborates that PfPDK1 acts in the cAMP/PKA signalling axis (upstream of PKA), consistent with the activation-loop phosphorylation model.","method":"In vitro drug-resistance selection + whole-genome sequencing","journal":"Science advances","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — independently replicates the PDK1–PKA pathway placement via a different selection pressure and a second lab's WGS data, but the functional consequence of the specific N324I mutation was not biochemically validated in this paper","pmids":["39642214"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2026,"finding":"In a competitive Kinobead pulldown assay from P. falciparum asexual blood-stage lysates, PfPDK1 (PF3D7_1121900) was identified as a direct binding target of the Chk1 inhibitor CHIR-124, with an apparent dissociation constant (Kd app) of 0.1 µM. However, conditional knockdown of PfPDK1 (using a GFP-DD degron tag) showed similar CHIR-124 IC50 values regardless of PfPDK1 protein levels, indicating that CHIR-124's parasiticidal activity is not mediated through PfPDK1 in whole cells.","method":"Kinobead competitive pulldown assay + conditional knockdown (GFP-DD degron) susceptibility assay","journal":"ACS chemical biology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — single lab, two orthogonal methods (biochemical binding assay + cellular knockdown), but the negative cellular result limits mechanistic conclusion to 'binds CHIR-124 in vitro but is not its cellular target'","pmids":["42287204"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":"NF54"}]}],"current_model":"PfPDK1 (PF3D7_1121900) functions as an essential upstream activator of the P. falciparum cAMP-dependent protein kinase A catalytic subunit (PfPKAc) by phosphorylating threonine 189 in the PfPKAc activation loop, a role established by suppressor-mutation mapping and targeted mutagenesis; PfPDK1 additionally influences gametocyte deformability, and mutations in its activation-loop region confer reduced susceptibility to PDEβ inhibitors, further corroborating its position in the cAMP/PKA signalling axis."},"narrative":{"mechanistic_narrative":"PfPDK1 (PF3D7_1121900) is an upstream protein kinase that activates the cAMP/PKA signalling axis in Plasmodium falciparum blood-stage parasites by phosphorylating the activation-loop threonine (T189) of the PKA catalytic subunit (PfPKAc), a role established through whole-genome sequencing of suppressor mutants selected to tolerate lethal PfPKAc overexpression together with targeted mutagenesis and conditional knockdown [PMID:34879056]. Its placement upstream of PKA is independently corroborated by the recovery of an activation-loop-proximal missense mutation (N324I) in parasites selected for resistance to a PDEβ inhibitor [PMID:39642214]. Beyond asexual signalling, conditional knockdown links PfPDK1 to regulation of gametocyte deformability in the sexual blood stages [PMID:34879056]. In vitro, PfPDK1 binds the Chk1 inhibitor CHIR-124 in a competitive Kinobead assay (Kd app ~0.1 µM), but knockdown does not alter CHIR-124 susceptibility, indicating it is not the cellular target of that compound [PMID:42287204]. No structural model of PfPDK1 or direct biochemical characterization of its catalytic mechanism beyond the T189 phosphorylation assignment has been reported in the available corpus.","teleology":[{"year":2021,"claim":"It was unknown what activates the essential PKA catalytic subunit in P. falciparum; identifying PfPDK1 as the activating kinase placed it at the head of the cAMP/PKA axis.","evidence":"WGS of suppressor mutants tolerating lethal PfPKAc overexpression, targeted mutagenesis of the PfPKAc T189 activation-loop residue, and conditional knockdown","pmids":["34879056"],"confidence":"High","gaps":["No in vitro reconstitution of PfPDK1 kinase activity on PfPKAc T189 with purified components","Upstream regulators and activation mechanism of PfPDK1 itself not defined","No structural basis for substrate recognition"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"claim":"Whether PfPDK1 functions beyond asexual signalling was untested; knockdown revealed a role in gametocyte deformability, extending its relevance to sexual blood stages.","evidence":"Conditional knockdown with phenotypic readout of gametocyte deformability","pmids":["34879056"],"confidence":"Medium","gaps":["No downstream molecular mechanism identified for the deformability phenotype","Unclear whether this phenotype acts through the PKA axis or an independent pathway"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"claim":"Independent confirmation of PfPDK1's pathway placement came from a different selection pressure, linking activation-loop-region mutations to altered cAMP/PKA signalling under drug challenge.","evidence":"In vitro selection for PDEβ inhibitor resistance plus WGS identifying the N324I substitution downstream of the activation loop","pmids":["39642214"],"confidence":"Medium","gaps":["Functional consequence of the specific N324I mutation not biochemically validated","Mechanism connecting PfPDK1 mutation to inhibitor resistance not resolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2026,"claim":"A candidate small-molecule interaction was tested; PfPDK1 binds CHIR-124 in vitro but this binding does not drive the compound's parasiticidal effect, refining understanding of its druggability.","evidence":"Competitive Kinobead pulldown (Kd app ~0.1 µM) plus GFP-DD degron conditional knockdown susceptibility assay","pmids":["42287204"],"confidence":"Medium","gaps":["The true cellular target of CHIR-124 remains unidentified","Negative cellular result limits conclusion to in vitro binding only"],"attribution":[{"species":"Plasmodium falciparum","strain":"NF54"}]},{"year":null,"claim":"The catalytic mechanism, structural basis, and full substrate repertoire of PfPDK1 beyond PfPKAc T189 remain undefined.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No purified-enzyme kinase assay or structure","No additional substrates characterized","Upstream activators of PfPDK1 unknown"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PFPKAC (PKA CATALYTIC SUBUNIT; SUBSTRATE PHOSPHORYLATED AT T189)"],"other_free_text":["Activates PfPKAc by phosphorylating activation-loop residue T189 [#0]","Activation-loop-proximal mutation N324I recovered under PDEβ inhibitor selection [#2]","Regulates gametocyte deformability in sexual blood stages [#1]","Binds Chk1 inhibitor CHIR-124 in vitro (Kd app ~0.1 µM) but is not its cellular target [#3]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"9108547","id":"PMC_9108547","title":"A putative Plasmodium falciparum exported serine/threonine protein kinase.","date":"1997","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/9108547","citation_count":41,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["serine/threonine protein kinase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34879056","id":"PMC_34879056","title":"The 3-phosphoinositide-dependent protein kinase 1 is an essential upstream activator of protein kinase A in malaria parasites.","date":"2021","source":"PLoS biology","url":"https://pubmed.ncbi.nlm.nih.gov/34879056","citation_count":18,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["3-phosphoinositide-dependent protein kinase 1","PfPDK1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"42287204","id":"","title":"The Human Chk1 Inhibitor CHIR-124 Shows Multistage Activity against the Human Malaria Parasite Plasmodium falciparum via Polypharmacological Inhibition of PfArk1 and Hemozoin Formation.","date":"2026","source":"ACS chemical biology","url":"https://pubmed.ncbi.nlm.nih.gov/42287204","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PDK1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39642214","id":"","title":"Inhibitors of malaria parasite cyclic nucleotide phosphodiesterases block asexual blood-stage development and mosquito transmission.","date":"2024","source":"Science advances","url":"https://pubmed.ncbi.nlm.nih.gov/39642214","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PDK1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38935780","id":"","title":"Activation loop phosphorylation and cGMP saturation of PKG regulate egress of malaria parasites.","date":"2024","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/38935780","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PDK1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38892332","id":"","title":"Post-Translational Modifications of Proteins of Malaria Parasites during the Life Cycle.","date":"2024","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/38892332","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PDK1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35961464","id":"","title":"Functional inactivation of Plasmodium falciparum glycogen synthase kinase GSK3 modulates erythrocyte invasion and blocks gametocyte maturation.","date":"2022","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/35961464","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PDK1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35909628","id":"","title":"MAPPINGS, a tool for network analysis of large phospho-signalling datasets: application to host erythrocyte response to Plasmodium infection.","date":"2022","source":"Current research in microbial sciences","url":"https://pubmed.ncbi.nlm.nih.gov/35909628","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PDK1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"37791074","id":"","title":"Regulation of phosphoinositide metabolism in Apicomplexan parasites.","date":"2023","source":"Frontiers in cell and developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/37791074","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PDK1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35453786","id":"","title":"Whole Genome Sequencing Contributions and Challenges in Disease Reduction Focused on Malaria.","date":"2022","source":"Biology","url":"https://pubmed.ncbi.nlm.nih.gov/35453786","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PDK1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"37915572","id":"","title":"Interactions between innate immunity and insulin signaling affect resistance to infection in insects.","date":"2023","source":"Frontiers in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/37915572","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PDK1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"20664791","id":"","title":"Activation of Akt signaling reduces the prevalence and intensity of malaria parasite infection and lifespan in Anopheles stephensi mosquitoes.","date":"2010","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/20664791","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PDK1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"20532217","id":"","title":"Protein kinase a dependent phosphorylation of apical membrane antigen 1 plays an important role in erythrocyte invasion by the malaria parasite.","date":"2010","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/20532217","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PDK1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":14588,"output_tokens":1408,"usd":0.032442,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6341,"output_tokens":2129,"usd":0.042465,"stage2_stop_reason":"end_turn"},"total_usd":0.074907,"stage1_batch_id":"msgbatch_01SRp5hyRc82zNjddxyCCXGk","stage2_batch_id":"msgbatch_01K3BTmBazRo3pRrMvyaPMTY","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2021,\n      \"finding\": \"PfPDK1 (PF3D7_1121900) is required to activate the catalytic subunit of protein kinase A (PfPKAc) in P. falciparum blood-stage parasites. Whole-genome sequencing of parasite mutants selected to tolerate lethal PfPKAc overexpression identified missense mutations exclusively in the gene encoding PfPDK1. Targeted mutagenesis confirmed that PfPDK1 activates PfPKAc, and that threonine 189 (T189) in the PfPKAc activation loop is the critical target residue phosphorylated by PfPDK1.\",\n      \"method\": \"Whole-genome sequencing of suppressor mutants + targeted mutagenesis (activation-loop phosphorylation) + conditional knockdown\",\n      \"journal\": \"PLoS biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (WGS suppressor screen, targeted mutagenesis of activation-loop residue, conditional knockdown) in a single rigorous study establishing the PDK1→PKAc T189 phosphorylation axis\",\n      \"pmids\": [\"34879056\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Conditional knockdown of PfPDK1 demonstrated that PfPDK1 is involved in regulating gametocyte deformability in P. falciparum, establishing a functional role for PfPDK1 in the sexual blood-stage forms.\",\n      \"method\": \"Conditional knockdown (cKD) with phenotypic readout of gametocyte deformability\",\n      \"journal\": \"PLoS biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — single lab, single conditional knockdown experiment with a defined cellular phenotype but no downstream molecular mechanism identified for this specific phenotype\",\n      \"pmids\": [\"34879056\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"In a drug-resistance selection experiment with a PDEβ inhibitor (5-benzyl compound SAL-0010003), whole-genome sequencing of resistant parasites detected a missense mutation in PfPDK1 (PF3D7_1121900): an asparagine-to-isoleucine substitution at position 324, immediately downstream of the activation loop. This finding independently corroborates that PfPDK1 acts in the cAMP/PKA signalling axis (upstream of PKA), consistent with the activation-loop phosphorylation model.\",\n      \"method\": \"In vitro drug-resistance selection + whole-genome sequencing\",\n      \"journal\": \"Science advances\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — independently replicates the PDK1–PKA pathway placement via a different selection pressure and a second lab's WGS data, but the functional consequence of the specific N324I mutation was not biochemically validated in this paper\",\n      \"pmids\": [\"39642214\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"In a competitive Kinobead pulldown assay from P. falciparum asexual blood-stage lysates, PfPDK1 (PF3D7_1121900) was identified as a direct binding target of the Chk1 inhibitor CHIR-124, with an apparent dissociation constant (Kd app) of 0.1 µM. However, conditional knockdown of PfPDK1 (using a GFP-DD degron tag) showed similar CHIR-124 IC50 values regardless of PfPDK1 protein levels, indicating that CHIR-124's parasiticidal activity is not mediated through PfPDK1 in whole cells.\",\n      \"method\": \"Kinobead competitive pulldown assay + conditional knockdown (GFP-DD degron) susceptibility assay\",\n      \"journal\": \"ACS chemical biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — single lab, two orthogonal methods (biochemical binding assay + cellular knockdown), but the negative cellular result limits mechanistic conclusion to 'binds CHIR-124 in vitro but is not its cellular target'\",\n      \"pmids\": [\"42287204\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"NF54\"}]\n    }\n  ],\n  \"current_model\": \"PfPDK1 (PF3D7_1121900) functions as an essential upstream activator of the P. falciparum cAMP-dependent protein kinase A catalytic subunit (PfPKAc) by phosphorylating threonine 189 in the PfPKAc activation loop, a role established by suppressor-mutation mapping and targeted mutagenesis; PfPDK1 additionally influences gametocyte deformability, and mutations in its activation-loop region confer reduced susceptibility to PDEβ inhibitors, further corroborating its position in the cAMP/PKA signalling axis.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PfPDK1 (PF3D7_1121900) is an upstream protein kinase that activates the cAMP/PKA signalling axis in Plasmodium falciparum blood-stage parasites by phosphorylating the activation-loop threonine (T189) of the PKA catalytic subunit (PfPKAc), a role established through whole-genome sequencing of suppressor mutants selected to tolerate lethal PfPKAc overexpression together with targeted mutagenesis and conditional knockdown [#0]. Its placement upstream of PKA is independently corroborated by the recovery of an activation-loop-proximal missense mutation (N324I) in parasites selected for resistance to a PDEβ inhibitor [#2]. Beyond asexual signalling, conditional knockdown links PfPDK1 to regulation of gametocyte deformability in the sexual blood stages [#1]. In vitro, PfPDK1 binds the Chk1 inhibitor CHIR-124 in a competitive Kinobead assay (Kd app ~0.1 µM), but knockdown does not alter CHIR-124 susceptibility, indicating it is not the cellular target of that compound [#3]. No structural model of PfPDK1 or direct biochemical characterization of its catalytic mechanism beyond the T189 phosphorylation assignment has been reported in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2021,\n      \"claim\": \"It was unknown what activates the essential PKA catalytic subunit in P. falciparum; identifying PfPDK1 as the activating kinase placed it at the head of the cAMP/PKA axis.\",\n      \"evidence\": \"WGS of suppressor mutants tolerating lethal PfPKAc overexpression, targeted mutagenesis of the PfPKAc T189 activation-loop residue, and conditional knockdown\",\n      \"pmids\": [\"34879056\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No in vitro reconstitution of PfPDK1 kinase activity on PfPKAc T189 with purified components\", \"Upstream regulators and activation mechanism of PfPDK1 itself not defined\", \"No structural basis for substrate recognition\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Whether PfPDK1 functions beyond asexual signalling was untested; knockdown revealed a role in gametocyte deformability, extending its relevance to sexual blood stages.\",\n      \"evidence\": \"Conditional knockdown with phenotypic readout of gametocyte deformability\",\n      \"pmids\": [\"34879056\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No downstream molecular mechanism identified for the deformability phenotype\", \"Unclear whether this phenotype acts through the PKA axis or an independent pathway\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Independent confirmation of PfPDK1's pathway placement came from a different selection pressure, linking activation-loop-region mutations to altered cAMP/PKA signalling under drug challenge.\",\n      \"evidence\": \"In vitro selection for PDEβ inhibitor resistance plus WGS identifying the N324I substitution downstream of the activation loop\",\n      \"pmids\": [\"39642214\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional consequence of the specific N324I mutation not biochemically validated\", \"Mechanism connecting PfPDK1 mutation to inhibitor resistance not resolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"A candidate small-molecule interaction was tested; PfPDK1 binds CHIR-124 in vitro but this binding does not drive the compound's parasiticidal effect, refining understanding of its druggability.\",\n      \"evidence\": \"Competitive Kinobead pulldown (Kd app ~0.1 µM) plus GFP-DD degron conditional knockdown susceptibility assay\",\n      \"pmids\": [\"42287204\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"The true cellular target of CHIR-124 remains unidentified\", \"Negative cellular result limits conclusion to in vitro binding only\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"NF54\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The catalytic mechanism, structural basis, and full substrate repertoire of PfPDK1 beyond PfPKAc T189 remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No purified-enzyme kinase assay or structure\", \"No additional substrates characterized\", \"Upstream activators of PfPDK1 unknown\"],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004672\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0004674\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0019901\", \"supporting_discovery_ids\": [0, 3]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0034199\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"PfPKAc (PKA catalytic subunit; substrate phosphorylated at T189)\"],\n    \"other_free_text\": [\n      \"Activates PfPKAc by phosphorylating activation-loop residue T189 [#0]\",\n      \"Activation-loop-proximal mutation N324I recovered under PDEβ inhibitor selection [#2]\",\n      \"Regulates gametocyte deformability in sexual blood stages [#1]\",\n      \"Binds Chk1 inhibitor CHIR-124 in vitro (Kd app ~0.1 µM) but is not its cellular target [#3]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1121900","name":null,"product":"3-phosphoinositide-dependent protein kinase 1","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0926400","name":null,"product":"serine/threonine protein kinase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0919600","name":null,"product":"3-phosphoinositide-dependent protein kinase 1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"PDK1","evaluation":null}