{"gene":"PF3D7_1444800","run_date":"2026-09-08T14:19:07","timeline":{"discoveries":[{"year":1998,"finding":"FBPA (PF3D7_1444800) is a class I fructose-1,6-bisphosphate aldolase that forms a homotetramer (80 kDa dimer per asymmetric unit). X-ray crystal structure at 3.0 Å resolution revealed a unique hydrophobic surface pocket resulting from amino acid changes and a single residue deletion relative to human aldolase, and reduced buried surface area in the tetramer interface compared to human aldolase.","method":"X-ray crystallography (crystal structure determination, R-factor 0.239, R-free 0.329, 3.0 Å resolution)","journal":"Biochemistry","confidence":"High","confidence_rationale":"Tier 1 / Moderate — crystal structure with defined resolution and R-factors, single study but direct structural method","pmids":["9521758"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2007,"finding":"FBPA (PF3D7_1444800) binds the C-terminal cytoplasmic tail of TRAP via an induced-fit mechanism: the penultimate Trp residue of TRAP inserts into a hydrophobic pocket formed exclusively by hydrophilic residues (two Arg, one Glu, one Gln) of FBPA; two Arg residues adopt new side-chain rotamers and a 25-residue helix-loop-helix subdomain shifts upon TRAP-tail binding. Mutagenesis of FBPA residues in and near this induced pocket decreased TRAP binding. The TRAP- and actin-binding sites on FBPA appear to overlap.","method":"X-ray crystallography (2.4 Å and 2.7 Å structures of FBPA co-crystallized with TRAP C-terminal hexapeptide) combined with site-directed mutagenesis of FBPA binding-site residues","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1 / Strong — high-resolution crystal structures plus mutagenesis validation in single rigorous study","pmids":["17426153"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":1990,"finding":"FBPA (PF3D7_1444800) is encoded by a single-copy gene interrupted by one intron; the protein (40,105 Da) was expressed in E. coli in enzymatically active form. In the parasite, an active soluble form localises to the cytoplasm, and an inactive form associates with the membrane fraction; phospholipase C digestion data suggest membrane association is mediated via a glycosylphosphatidylinositol (GPI) anchor.","method":"Gene cloning and expression in E. coli (enzymatic activity assay), cell fractionation, phospholipase C digestion, immunoblotting with antisera against residues 9–96","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — enzymatic activity confirmed by recombinant expression; membrane association inferred from fractionation and phospholipase C digestion in single study","pmids":["2190085"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":1992,"finding":"In Plasmodium berghei, two aldolase isoenzymes (ALDO-1 and ALDO-2) are expressed in a stage-specific manner: ALDO-1 (virtually identical in sequence to P. falciparum FBPA) is detected in sporozoite stages, while ALDO-2 is expressed in blood stages. Recombinant ALDO-2 expressed in E. coli is enzymatically active; Km and Vmax constants for FBP and FMP differ from mammalian isoenzymes and cannot be assigned to any known mammalian class.","method":"Gene cloning, recombinant expression in E. coli with enzymatic kinetic assays (Km/Vmax), immunoblotting with stage-specific antibodies","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — enzymatic characterisation of recombinant protein plus stage-specific immunodetection, single study","pmids":["1625704"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2005,"finding":"FBPA (PF3D7_1444800) is present in P. falciparum merozoites and its in vitro binding to the cytoplasmic tail of the merozoite adhesin MTRAP (a TRAP-family micronemal protein) was demonstrated, placing FBPA as the link between MTRAP and the actin-myosin motor complex in erythrocyte invasion.","method":"In vitro binding assay (cytoplasmic tail of MTRAP binding to aldolase), immunofluorescence/co-localisation","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — in vitro binding assay, replicated across two adhesins (TRAP family), but single lab without full mechanistic dissection","pmids":["16321976"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2012,"finding":"FBPA (PF3D7_1444800) binds the cytoplasmic tails of select P. falciparum merozoite RH (reticulocyte homology) ligands (e.g. RH2b but not RH2a) at affinities similar to TRAP, dependent on an aromatic residue (phenylalanine or tyrosine, not tryptophan) flanked by negatively charged amino acids. A 2.5 Å X-ray crystal structure of FBPA with the RH2b peptide showed the binding site is near the TRAP-binding site. FBPA did not similarly bind tested DBL-family cytoplasmic tails.","method":"Surface plasmon resonance, X-ray crystallography (2.5 Å), peptide binding assays, site-directed analysis of aromatic residue requirements","journal":"mBio","confidence":"High","confidence_rationale":"Tier 1 / Moderate — crystal structure plus SPR quantitative binding, two orthogonal methods in single study","pmids":["22991428"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"finding":"FBPA (PF3D7_1444800) binds both rabbit and P. falciparum actin (filamentous F-actin and globular G-actin) with high and similar affinity, as measured by biolayer interferometry, and this interaction was confirmed by co-sedimentation assay. FBPA binding promotes actin polymerization, indicating the interaction is more than passive binding.","method":"Biolayer interferometry (quantitative binding), co-sedimentation assay, actin polymerization assay","journal":"Molecular and biochemical parasitology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — two orthogonal binding methods (biolayer interferometry + co-sedimentation) plus functional polymerization assay, single lab","pmids":["25261592"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"finding":"A small molecule (compound 24) that stabilizes the FBPA–TRAP complex inhibits gliding motility and host cell invasion. A high-resolution ternary X-ray crystal structure of FBPA–TRAP–compound 24 confirms the binding mode at the FBPA–TRAP interface. Liver cell invasion was reduced by ~95% in the presence of compound 24, demonstrating that the FBPA–TRAP interaction is functionally required for invasion.","method":"Virtual library screening, biochemical/biophysical compound characterisation, ternary X-ray crystal structure, in vitro parasite gliding and invasion assays","journal":"Malaria journal","confidence":"High","confidence_rationale":"Tier 1 / Moderate — ternary crystal structure plus functional invasion assay with quantified inhibition, single lab with multiple orthogonal methods","pmids":["26289816"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"finding":"FBPA (PF3D7_1444800) binds the cytoplasmic tail domains (CTDs) of TRAP, MTRAP, AMA1, and members of the EBL and RH protein families; MTRAP CTD binding requires more than the C-terminal six residues and single amino acid substitutions in MTRAP CTD abolished aldolase binding. MTRAP CTD is phosphorylated in vitro by CDPK1 and PKA, and phosphorylation increases FBPA binding affinity ~10-fold. MTRAP competed with AMA1 and RH4 for overlapping binding sites on FBPA. No phosphorylation of MTRAP was detected in asexual blood-stage parasites expressing GFP-tagged MTRAP.","method":"Direct in vitro binding assay (quantitative), site-directed mutagenesis of MTRAP CTD, in vitro kinase assays (CDPK1, PKA), affinity measurements, competition binding assay, GFP-tagging and purification of MTRAP from parasites with phosphorylation analysis","journal":"PloS one","confidence":"High","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (binding assay, mutagenesis, kinase assay, competition assay, in-parasite protein analysis) in single study","pmids":["27607074"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":1994,"finding":"In Plasmodium berghei, the aldo-2 mRNA is processed by pre-mRNA splicing that appends an AUG initiation codon to the exon; a UAG codon at the beginning of the aldo-2 coding sequence is not used as an initiation codon in vitro. Substantially unspliced (partially spliced) aldo-2 precursor mRNA accumulates in vivo, which explains previously isolated P. falciparum aldolase cDNA clones starting with a stop codon.","method":"Reverse-PCR cDNA sequencing, in vitro translation, Northern blot analysis","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — cDNA sequencing plus in vitro translation and Northern blot, single study, applies to P. berghei aldo-2 (not directly to PF3D7_1444800)","pmids":["8008025"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"FBPA (PF3D7_1444800) is a homotetrameric class I fructose-1,6-bisphosphate aldolase that functions dually as a glycolytic enzyme in the parasite cytoplasm and as a non-enzymatic scaffold in the glideosome invasion motor: it physically bridges the cytoplasmic tails of TRAP-family adhesins and other invasion ligands (MTRAP, AMA1, EBL/RH family members) to F-actin via an induced-fit binding mechanism at an overlapping site, promotes actin polymerization, and this interaction—which is potentiated ~10-fold by phosphorylation of the ligand CTD by CDPK1/PKA—is essential for gliding motility and host-cell invasion."},"narrative":{"mechanistic_narrative":"FBPA (PF3D7_1444800) is a class I fructose-1,6-bisphosphate aldolase that acts both as a glycolytic enzyme and as a structural bridge in the Plasmodium falciparum invasion motor [PMID:9521758, PMID:16321976]. It is a single-copy gene product that forms a homotetramer, and its crystal structure diverges from human aldolase through a unique hydrophobic surface pocket and a reduced tetramer interface [PMID:9521758]. A soluble, enzymatically active form localizes to the parasite cytoplasm, while an inactive membrane-associated form has also been detected [PMID:2190085]. Beyond its catalytic role, FBPA physically links the actin-myosin motor to invasion adhesins: it binds the C-terminal cytoplasmic tails of the TRAP-family adhesins TRAP and MTRAP, of AMA1, and of members of the EBL and RH ligand families through an induced-fit mechanism in which an aromatic residue of the ligand tail inserts into a hydrophobic pocket, causing arginine rotamer changes and a helix-loop-helix subdomain shift [PMID:17426153, PMID:16321976, PMID:22991428, PMID:27607074]. These adhesin tails compete for overlapping binding sites on FBPA, and phosphorylation of the MTRAP tail by CDPK1 and PKA increases FBPA binding affinity ~10-fold [PMID:27607074]. FBPA simultaneously binds both G- and F-actin with high affinity and promotes actin polymerization, providing the second half of the mechanical link [PMID:25261592]. The FBPA-TRAP interaction is functionally required for motility: a small molecule stabilizing the complex reduces liver-cell invasion by ~95% and blocks gliding [PMID:26289816].","teleology":[{"year":1990,"claim":"Establishing that FBPA is a genuine catalytic aldolase defined its baseline identity before any moonlighting role was known.","evidence":"gene cloning and expression of enzymatically active recombinant protein in E. coli, with cell fractionation showing cytoplasmic and membrane-associated forms","pmids":["2190085"],"confidence":"Medium","gaps":["GPI-anchor-mediated membrane association inferred from phospholipase C digestion, not directly demonstrated","functional significance of the inactive membrane form unresolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":1992,"claim":"Kinetic characterization showed the parasite aldolase is enzymatically distinct from mammalian isoenzymes, indicating a divergent enzyme rather than a host contaminant.","evidence":"recombinant expression and Km/Vmax kinetics of P. berghei aldolase isoenzymes with stage-specific immunodetection","pmids":["1625704"],"confidence":"Medium","gaps":["performed on P. berghei isoenzymes, not directly on PF3D7_1444800","stage-specific expression pattern not mapped in P. falciparum"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":1994,"claim":"Defining the pre-mRNA splicing that supplies the initiation codon clarified prior anomalous cDNA clones and the gene architecture of the aldolase locus.","evidence":"reverse-PCR cDNA sequencing, in vitro translation, and Northern blot in P. berghei aldo-2","pmids":["8008025"],"confidence":"Medium","gaps":["shown for P. berghei aldo-2, not PF3D7_1444800","regulatory role of accumulated unspliced precursor unknown"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":1998,"claim":"The crystal structure revealed parasite-specific features—a unique hydrophobic surface pocket and altered tetramer interface—establishing structural targets distinguishing FBPA from human aldolase.","evidence":"X-ray crystallography at 3.0 Å (homotetramer)","pmids":["9521758"],"confidence":"High","gaps":["functional role of the unique surface pocket not addressed at this stage","no ligand bound"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2005,"claim":"Demonstrating FBPA binding to the MTRAP cytoplasmic tail positioned it as the physical bridge between an invasion adhesin and the actin-myosin motor in merozoites.","evidence":"in vitro binding assay of MTRAP cytoplasmic tail to aldolase plus co-localization","pmids":["16321976"],"confidence":"Medium","gaps":["binding not yet linked to actin at structural resolution","in vivo requirement not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2007,"claim":"Co-crystallization with the TRAP tail defined the induced-fit binding mechanism and revealed that the adhesin- and actin-binding sites overlap, explaining how one aldolase could couple two partners.","evidence":"X-ray structures at 2.4 and 2.7 Å of FBPA with TRAP hexapeptide plus site-directed mutagenesis","pmids":["17426153"],"confidence":"High","gaps":["actin binding at the overlapping site inferred, not co-crystallized","consequence for catalytic activity during binding not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2012,"claim":"Extending the binding repertoire to RH-family ligand tails defined the sequence rules (an aromatic residue flanked by acidic residues) and showed selectivity among ligands.","evidence":"surface plasmon resonance, 2.5 Å crystal structure with RH2b peptide, aromatic-residue analysis","pmids":["22991428"],"confidence":"High","gaps":["basis for selectivity (RH2b vs RH2a, DBL exclusion) not fully mechanistically explained","in vivo relevance of each ligand interaction untested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"claim":"Quantifying high-affinity binding to both G- and F-actin and showing FBPA promotes actin polymerization established that FBPA actively contributes to the actin half of the motor linkage.","evidence":"biolayer interferometry, co-sedimentation, and actin polymerization assays","pmids":["25261592"],"confidence":"High","gaps":["structural basis of actin binding not resolved","polymerization effect not tested in intact motor context"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"claim":"A small molecule stabilizing the FBPA-TRAP complex blocking invasion provided direct functional proof that this protein-protein interaction is required for motility and invasion.","evidence":"virtual screening, ternary FBPA-TRAP-compound 24 crystal structure, gliding and liver-cell invasion assays (~95% reduction)","pmids":["26289816"],"confidence":"High","gaps":["genetic ablation of the interaction not performed","distinction between glycolytic and scaffold contributions to the phenotype not resolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"claim":"Mapping the full adhesin binding set, defining CTD sequence requirements, and demonstrating phosphorylation-enhanced binding integrated FBPA into a regulatable hub coupling multiple ligands to actin.","evidence":"quantitative binding, CTD mutagenesis, CDPK1/PKA kinase assays, competition assays, and in-parasite MTRAP phosphorylation analysis","pmids":["27607074"],"confidence":"High","gaps":["MTRAP phosphorylation not detected in asexual blood-stage parasites, leaving the in vivo trigger unresolved","physiological hierarchy among competing ligands unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether the glycolytic and scaffolding functions of FBPA can be genetically separated, and how binding is regulated during native invasion, remains open.","evidence":"","pmids":[],"confidence":"Medium","gaps":["no genetic separation-of-function mutant reported","in vivo phosphorylation trigger for enhanced binding not established","functional role of the membrane-associated inactive form unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["FBPA homotetramer","FBPA-TRAP cytoplasmic tail complex","FBPA-MTRAP cytoplasmic tail complex","FBPA-RH2b peptide complex","FBPA-TRAP-compound 24 ternary complex","glideosome actin-myosin invasion motor link"],"partners":["TRAP (CYTOPLASMIC TAIL)","MTRAP (CYTOPLASMIC TAIL)","AMA1 (CYTOPLASMIC TAIL)","EBL-FAMILY LIGAND CYTOPLASMIC TAILS","RH-FAMILY LIGAND CYTOPLASMIC TAILS (E.G. RH2B, RH4)","F-ACTIN","G-ACTIN","CDPK1 (PHOSPHORYLATES MTRAP CTD)","PKA (PHOSPHORYLATES MTRAP CTD)"],"other_free_text":["Ligand cytoplasmic tail binding uses an induced-fit mechanism in which an aromatic residue (Trp for TRAP; Phe/Tyr for RH2b) inserts into a hydrophobic pocket of FBPA [#1, #5].","Adhesin- and actin-binding sites on FBPA overlap, and competing ligands (MTRAP, AMA1, RH4) share overlapping binding sites [#1, #8].","Phosphorylation of the MTRAP CTD increases FBPA binding affinity ~10-fold, but MTRAP phosphorylation was not detected in asexual blood-stage parasites [#8].","P. falciparum FBPA is structurally distinct from human aldolase (unique hydrophobic surface pocket, reduced tetramer interface), a divergence exploited by an invasion-blocking small molecule [#0, #7].","In P. berghei, aldolase exists as stage-specific isoenzymes (ALDO-1/ALDO-2), with ALDO-1 nearly identical in sequence to P. falciparum FBPA [#3]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"16321976","id":"PMC_16321976","title":"A conserved molecular motor drives cell invasion and gliding motility across malaria life cycle stages and other apicomplexan parasites.","date":"2005","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/16321976","citation_count":291,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"17426153","id":"PMC_17426153","title":"Aldolase provides an unusual binding site for thrombospondin-related anonymous protein in the invasion machinery of the malaria parasite.","date":"2007","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/17426153","citation_count":67,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"9521758","id":"PMC_9521758","title":"Crystal structure of fructose-1,6-bisphosphate aldolase from the human malaria parasite Plasmodium falciparum.","date":"1998","source":"Biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/9521758","citation_count":67,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"2190085","id":"PMC_2190085","title":"Plasmodium falciparum aldolase: gene structure and localization.","date":"1990","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/2190085","citation_count":59,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["fructose-bisphosphate aldolase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"1625704","id":"PMC_1625704","title":"Stage-specific expression of aldolase isoenzymes in the rodent malaria parasite Plasmodium berghei.","date":"1992","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/1625704","citation_count":24,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ALDO2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"26289816","id":"PMC_26289816","title":"Inhibition by stabilization: targeting the Plasmodium falciparum aldolase-TRAP complex.","date":"2015","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/26289816","citation_count":23,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25261592","id":"PMC_25261592","title":"Plasmodium falciparum aldolase and the C-terminal cytoplasmic domain of certain apical organellar proteins promote actin polymerization.","date":"2014","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/25261592","citation_count":15,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"23339668","id":"PMC_23339668","title":"PfHPRT: a new biomarker candidate of acute Plasmodium falciparum infection.","date":"2013","source":"Journal of proteome research","url":"https://pubmed.ncbi.nlm.nih.gov/23339668","citation_count":14,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["fructose-bisphosphate aldolase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"22991428","id":"PMC_22991428","title":"Binding of aldolase and glyceraldehyde-3-phosphate dehydrogenase to the cytoplasmic tails of Plasmodium falciparum merozoite duffy binding-like and reticulocyte homology ligands.","date":"2012","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/22991428","citation_count":13,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"27607074","id":"PMC_27607074","title":"The Binding of Plasmodium falciparum Adhesins and Erythrocyte Invasion Proteins to Aldolase Is Enhanced by Phosphorylation.","date":"2016","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/27607074","citation_count":7,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25183269","id":"PMC_25183269","title":"Proteomics analysis of antimalarial targets of Garcinia mangostana Linn.","date":"2014","source":"Asian Pacific journal of tropical biomedicine","url":"https://pubmed.ncbi.nlm.nih.gov/25183269","citation_count":4,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["fructose-bisphosphate aldolase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"8008025","id":"PMC_8008025","title":"Regular initiation of translation of Plasmodium berghei aldolase-2 after pre-mRNA splicing.","date":"1994","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/8008025","citation_count":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ALDO2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":9153,"output_tokens":3286,"usd":0.038374,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":9043,"output_tokens":4344,"usd":0.076908,"stage2_stop_reason":"end_turn"},"total_usd":0.115282,"stage1_batch_id":"msgbatch_011BPjN2BL33F8cJXD1r7V7T","stage2_batch_id":"msgbatch_01Qwg6vP7qxkpL6Gsc7tajsb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1998,\n      \"finding\": \"FBPA (PF3D7_1444800) is a class I fructose-1,6-bisphosphate aldolase that forms a homotetramer (80 kDa dimer per asymmetric unit). X-ray crystal structure at 3.0 Å resolution revealed a unique hydrophobic surface pocket resulting from amino acid changes and a single residue deletion relative to human aldolase, and reduced buried surface area in the tetramer interface compared to human aldolase.\",\n      \"method\": \"X-ray crystallography (crystal structure determination, R-factor 0.239, R-free 0.329, 3.0 Å resolution)\",\n      \"journal\": \"Biochemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — crystal structure with defined resolution and R-factors, single study but direct structural method\",\n      \"pmids\": [\"9521758\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"FBPA (PF3D7_1444800) binds the C-terminal cytoplasmic tail of TRAP via an induced-fit mechanism: the penultimate Trp residue of TRAP inserts into a hydrophobic pocket formed exclusively by hydrophilic residues (two Arg, one Glu, one Gln) of FBPA; two Arg residues adopt new side-chain rotamers and a 25-residue helix-loop-helix subdomain shifts upon TRAP-tail binding. Mutagenesis of FBPA residues in and near this induced pocket decreased TRAP binding. The TRAP- and actin-binding sites on FBPA appear to overlap.\",\n      \"method\": \"X-ray crystallography (2.4 Å and 2.7 Å structures of FBPA co-crystallized with TRAP C-terminal hexapeptide) combined with site-directed mutagenesis of FBPA binding-site residues\",\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 crystal structures plus mutagenesis validation in single rigorous study\",\n      \"pmids\": [\"17426153\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 1990,\n      \"finding\": \"FBPA (PF3D7_1444800) is encoded by a single-copy gene interrupted by one intron; the protein (40,105 Da) was expressed in E. coli in enzymatically active form. In the parasite, an active soluble form localises to the cytoplasm, and an inactive form associates with the membrane fraction; phospholipase C digestion data suggest membrane association is mediated via a glycosylphosphatidylinositol (GPI) anchor.\",\n      \"method\": \"Gene cloning and expression in E. coli (enzymatic activity assay), cell fractionation, phospholipase C digestion, immunoblotting with antisera against residues 9–96\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — enzymatic activity confirmed by recombinant expression; membrane association inferred from fractionation and phospholipase C digestion in single study\",\n      \"pmids\": [\"2190085\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 1992,\n      \"finding\": \"In Plasmodium berghei, two aldolase isoenzymes (ALDO-1 and ALDO-2) are expressed in a stage-specific manner: ALDO-1 (virtually identical in sequence to P. falciparum FBPA) is detected in sporozoite stages, while ALDO-2 is expressed in blood stages. Recombinant ALDO-2 expressed in E. coli is enzymatically active; Km and Vmax constants for FBP and FMP differ from mammalian isoenzymes and cannot be assigned to any known mammalian class.\",\n      \"method\": \"Gene cloning, recombinant expression in E. coli with enzymatic kinetic assays (Km/Vmax), immunoblotting with stage-specific antibodies\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — enzymatic characterisation of recombinant protein plus stage-specific immunodetection, single study\",\n      \"pmids\": [\"1625704\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"FBPA (PF3D7_1444800) is present in P. falciparum merozoites and its in vitro binding to the cytoplasmic tail of the merozoite adhesin MTRAP (a TRAP-family micronemal protein) was demonstrated, placing FBPA as the link between MTRAP and the actin-myosin motor complex in erythrocyte invasion.\",\n      \"method\": \"In vitro binding assay (cytoplasmic tail of MTRAP binding to aldolase), immunofluorescence/co-localisation\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — in vitro binding assay, replicated across two adhesins (TRAP family), but single lab without full mechanistic dissection\",\n      \"pmids\": [\"16321976\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"FBPA (PF3D7_1444800) binds the cytoplasmic tails of select P. falciparum merozoite RH (reticulocyte homology) ligands (e.g. RH2b but not RH2a) at affinities similar to TRAP, dependent on an aromatic residue (phenylalanine or tyrosine, not tryptophan) flanked by negatively charged amino acids. A 2.5 Å X-ray crystal structure of FBPA with the RH2b peptide showed the binding site is near the TRAP-binding site. FBPA did not similarly bind tested DBL-family cytoplasmic tails.\",\n      \"method\": \"Surface plasmon resonance, X-ray crystallography (2.5 Å), peptide binding assays, site-directed analysis of aromatic residue requirements\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — crystal structure plus SPR quantitative binding, two orthogonal methods in single study\",\n      \"pmids\": [\"22991428\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"FBPA (PF3D7_1444800) binds both rabbit and P. falciparum actin (filamentous F-actin and globular G-actin) with high and similar affinity, as measured by biolayer interferometry, and this interaction was confirmed by co-sedimentation assay. FBPA binding promotes actin polymerization, indicating the interaction is more than passive binding.\",\n      \"method\": \"Biolayer interferometry (quantitative binding), co-sedimentation assay, actin polymerization assay\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — two orthogonal binding methods (biolayer interferometry + co-sedimentation) plus functional polymerization assay, single lab\",\n      \"pmids\": [\"25261592\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"A small molecule (compound 24) that stabilizes the FBPA–TRAP complex inhibits gliding motility and host cell invasion. A high-resolution ternary X-ray crystal structure of FBPA–TRAP–compound 24 confirms the binding mode at the FBPA–TRAP interface. Liver cell invasion was reduced by ~95% in the presence of compound 24, demonstrating that the FBPA–TRAP interaction is functionally required for invasion.\",\n      \"method\": \"Virtual library screening, biochemical/biophysical compound characterisation, ternary X-ray crystal structure, in vitro parasite gliding and invasion assays\",\n      \"journal\": \"Malaria journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — ternary crystal structure plus functional invasion assay with quantified inhibition, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"26289816\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"FBPA (PF3D7_1444800) binds the cytoplasmic tail domains (CTDs) of TRAP, MTRAP, AMA1, and members of the EBL and RH protein families; MTRAP CTD binding requires more than the C-terminal six residues and single amino acid substitutions in MTRAP CTD abolished aldolase binding. MTRAP CTD is phosphorylated in vitro by CDPK1 and PKA, and phosphorylation increases FBPA binding affinity ~10-fold. MTRAP competed with AMA1 and RH4 for overlapping binding sites on FBPA. No phosphorylation of MTRAP was detected in asexual blood-stage parasites expressing GFP-tagged MTRAP.\",\n      \"method\": \"Direct in vitro binding assay (quantitative), site-directed mutagenesis of MTRAP CTD, in vitro kinase assays (CDPK1, PKA), affinity measurements, competition binding assay, GFP-tagging and purification of MTRAP from parasites with phosphorylation analysis\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (binding assay, mutagenesis, kinase assay, competition assay, in-parasite protein analysis) in single study\",\n      \"pmids\": [\"27607074\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 1994,\n      \"finding\": \"In Plasmodium berghei, the aldo-2 mRNA is processed by pre-mRNA splicing that appends an AUG initiation codon to the exon; a UAG codon at the beginning of the aldo-2 coding sequence is not used as an initiation codon in vitro. Substantially unspliced (partially spliced) aldo-2 precursor mRNA accumulates in vivo, which explains previously isolated P. falciparum aldolase cDNA clones starting with a stop codon.\",\n      \"method\": \"Reverse-PCR cDNA sequencing, in vitro translation, Northern blot analysis\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — cDNA sequencing plus in vitro translation and Northern blot, single study, applies to P. berghei aldo-2 (not directly to PF3D7_1444800)\",\n      \"pmids\": [\"8008025\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"FBPA (PF3D7_1444800) is a homotetrameric class I fructose-1,6-bisphosphate aldolase that functions dually as a glycolytic enzyme in the parasite cytoplasm and as a non-enzymatic scaffold in the glideosome invasion motor: it physically bridges the cytoplasmic tails of TRAP-family adhesins and other invasion ligands (MTRAP, AMA1, EBL/RH family members) to F-actin via an induced-fit binding mechanism at an overlapping site, promotes actin polymerization, and this interaction—which is potentiated ~10-fold by phosphorylation of the ligand CTD by CDPK1/PKA—is essential for gliding motility and host-cell invasion.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"FBPA (PF3D7_1444800) is a class I fructose-1,6-bisphosphate aldolase that acts both as a glycolytic enzyme and as a structural bridge in the Plasmodium falciparum invasion motor [#0, #4]. It is a single-copy gene product that forms a homotetramer, and its crystal structure diverges from human aldolase through a unique hydrophobic surface pocket and a reduced tetramer interface [#0]. A soluble, enzymatically active form localizes to the parasite cytoplasm, while an inactive membrane-associated form has also been detected [#2]. Beyond its catalytic role, FBPA physically links the actin-myosin motor to invasion adhesins: it binds the C-terminal cytoplasmic tails of the TRAP-family adhesins TRAP and MTRAP, of AMA1, and of members of the EBL and RH ligand families through an induced-fit mechanism in which an aromatic residue of the ligand tail inserts into a hydrophobic pocket, causing arginine rotamer changes and a helix-loop-helix subdomain shift [#1, #4, #5, #8]. These adhesin tails compete for overlapping binding sites on FBPA, and phosphorylation of the MTRAP tail by CDPK1 and PKA increases FBPA binding affinity ~10-fold [#8]. FBPA simultaneously binds both G- and F-actin with high affinity and promotes actin polymerization, providing the second half of the mechanical link [#6]. The FBPA-TRAP interaction is functionally required for motility: a small molecule stabilizing the complex reduces liver-cell invasion by ~95% and blocks gliding [#7].\",\n  \"teleology\": [\n    {\n      \"year\": 1990,\n      \"claim\": \"Establishing that FBPA is a genuine catalytic aldolase defined its baseline identity before any moonlighting role was known.\",\n      \"evidence\": \"gene cloning and expression of enzymatically active recombinant protein in E. coli, with cell fractionation showing cytoplasmic and membrane-associated forms\",\n      \"pmids\": [\"2190085\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"GPI-anchor-mediated membrane association inferred from phospholipase C digestion, not directly demonstrated\", \"functional significance of the inactive membrane form unresolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 1992,\n      \"claim\": \"Kinetic characterization showed the parasite aldolase is enzymatically distinct from mammalian isoenzymes, indicating a divergent enzyme rather than a host contaminant.\",\n      \"evidence\": \"recombinant expression and Km/Vmax kinetics of P. berghei aldolase isoenzymes with stage-specific immunodetection\",\n      \"pmids\": [\"1625704\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"performed on P. berghei isoenzymes, not directly on PF3D7_1444800\", \"stage-specific expression pattern not mapped in P. falciparum\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 1994,\n      \"claim\": \"Defining the pre-mRNA splicing that supplies the initiation codon clarified prior anomalous cDNA clones and the gene architecture of the aldolase locus.\",\n      \"evidence\": \"reverse-PCR cDNA sequencing, in vitro translation, and Northern blot in P. berghei aldo-2\",\n      \"pmids\": [\"8008025\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"shown for P. berghei aldo-2, not PF3D7_1444800\", \"regulatory role of accumulated unspliced precursor unknown\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 1998,\n      \"claim\": \"The crystal structure revealed parasite-specific features—a unique hydrophobic surface pocket and altered tetramer interface—establishing structural targets distinguishing FBPA from human aldolase.\",\n      \"evidence\": \"X-ray crystallography at 3.0 Å (homotetramer)\",\n      \"pmids\": [\"9521758\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"functional role of the unique surface pocket not addressed at this stage\", \"no ligand bound\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Demonstrating FBPA binding to the MTRAP cytoplasmic tail positioned it as the physical bridge between an invasion adhesin and the actin-myosin motor in merozoites.\",\n      \"evidence\": \"in vitro binding assay of MTRAP cytoplasmic tail to aldolase plus co-localization\",\n      \"pmids\": [\"16321976\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"binding not yet linked to actin at structural resolution\", \"in vivo requirement not tested\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Co-crystallization with the TRAP tail defined the induced-fit binding mechanism and revealed that the adhesin- and actin-binding sites overlap, explaining how one aldolase could couple two partners.\",\n      \"evidence\": \"X-ray structures at 2.4 and 2.7 Å of FBPA with TRAP hexapeptide plus site-directed mutagenesis\",\n      \"pmids\": [\"17426153\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"actin binding at the overlapping site inferred, not co-crystallized\", \"consequence for catalytic activity during binding not defined\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Extending the binding repertoire to RH-family ligand tails defined the sequence rules (an aromatic residue flanked by acidic residues) and showed selectivity among ligands.\",\n      \"evidence\": \"surface plasmon resonance, 2.5 Å crystal structure with RH2b peptide, aromatic-residue analysis\",\n      \"pmids\": [\"22991428\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"basis for selectivity (RH2b vs RH2a, DBL exclusion) not fully mechanistically explained\", \"in vivo relevance of each ligand interaction untested\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Quantifying high-affinity binding to both G- and F-actin and showing FBPA promotes actin polymerization established that FBPA actively contributes to the actin half of the motor linkage.\",\n      \"evidence\": \"biolayer interferometry, co-sedimentation, and actin polymerization assays\",\n      \"pmids\": [\"25261592\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"structural basis of actin binding not resolved\", \"polymerization effect not tested in intact motor context\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"A small molecule stabilizing the FBPA-TRAP complex blocking invasion provided direct functional proof that this protein-protein interaction is required for motility and invasion.\",\n      \"evidence\": \"virtual screening, ternary FBPA-TRAP-compound 24 crystal structure, gliding and liver-cell invasion assays (~95% reduction)\",\n      \"pmids\": [\"26289816\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"genetic ablation of the interaction not performed\", \"distinction between glycolytic and scaffold contributions to the phenotype not resolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Mapping the full adhesin binding set, defining CTD sequence requirements, and demonstrating phosphorylation-enhanced binding integrated FBPA into a regulatable hub coupling multiple ligands to actin.\",\n      \"evidence\": \"quantitative binding, CTD mutagenesis, CDPK1/PKA kinase assays, competition assays, and in-parasite MTRAP phosphorylation analysis\",\n      \"pmids\": [\"27607074\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"MTRAP phosphorylation not detected in asexual blood-stage parasites, leaving the in vivo trigger unresolved\", \"physiological hierarchy among competing ligands unknown\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether the glycolytic and scaffolding functions of FBPA can be genetically separated, and how binding is regulated during native invasion, remains open.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"no genetic separation-of-function mutant reported\", \"in vivo phosphorylation trigger for enhanced binding not established\", \"functional role of the membrane-associated inactive form unknown\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004332\", \"supporting_discovery_ids\": [0, 2, 3]},\n      {\"term_id\": \"GO:0051015\", \"supporting_discovery_ids\": [6]},\n      {\"term_id\": \"GO:0030674\", \"supporting_discovery_ids\": [1, 4, 5, 8]},\n      {\"term_id\": \"GO:0051017\", \"supporting_discovery_ids\": [6]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"GO:0016020\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006096\", \"supporting_discovery_ids\": [0, 2, 3]},\n      {\"term_id\": \"GO:0071827\", \"supporting_discovery_ids\": [6]},\n      {\"term_id\": \"GO:0006909\", \"supporting_discovery_ids\": [4, 7, 8]}\n    ],\n    \"complexes\": [\n      \"FBPA homotetramer\",\n      \"FBPA-TRAP cytoplasmic tail complex\",\n      \"FBPA-MTRAP cytoplasmic tail complex\",\n      \"FBPA-RH2b peptide complex\",\n      \"FBPA-TRAP-compound 24 ternary complex\",\n      \"glideosome actin-myosin invasion motor link\"\n    ],\n    \"partners\": [\n      \"TRAP (cytoplasmic tail)\",\n      \"MTRAP (cytoplasmic tail)\",\n      \"AMA1 (cytoplasmic tail)\",\n      \"EBL-family ligand cytoplasmic tails\",\n      \"RH-family ligand cytoplasmic tails (e.g. RH2b, RH4)\",\n      \"F-actin\",\n      \"G-actin\",\n      \"CDPK1 (phosphorylates MTRAP CTD)\",\n      \"PKA (phosphorylates MTRAP CTD)\"\n    ],\n    \"other_free_text\": [\n      \"Ligand cytoplasmic tail binding uses an induced-fit mechanism in which an aromatic residue (Trp for TRAP; Phe/Tyr for RH2b) inserts into a hydrophobic pocket of FBPA [#1, #5].\",\n      \"Adhesin- and actin-binding sites on FBPA overlap, and competing ligands (MTRAP, AMA1, RH4) share overlapping binding sites [#1, #8].\",\n      \"Phosphorylation of the MTRAP CTD increases FBPA binding affinity ~10-fold, but MTRAP phosphorylation was not detected in asexual blood-stage parasites [#8].\",\n      \"P. falciparum FBPA is structurally distinct from human aldolase (unique hydrophobic surface pocket, reduced tetramer interface), a divergence exploited by an invasion-blocking small molecule [#0, #7].\",\n      \"In P. berghei, aldolase exists as stage-specific isoenzymes (ALDO-1/ALDO-2), with ALDO-1 nearly identical in sequence to P. falciparum FBPA [#3].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1444800","name":null,"product":"fructose-bisphosphate aldolase","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1308600","name":null,"product":"fructose-bisphosphate aldolase 2","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1237500","name":null,"product":"fructose-bisphosphate aldolase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"FBPA","evaluation":null}