{"gene":"PF3D7_1323000","run_date":"2026-09-08T14:19:06","timeline":{"discoveries":[{"year":1998,"finding":"FabZ (PF3D7_1323000) is a nuclear-encoded gene whose protein product bears an N-terminal presequence consistent with apicoplast targeting, and immunolocalization data (using ACP as a proxy for the FAS pathway) indicates that FabZ very probably localizes to the apicoplast of P. falciparum, implicating fatty acid biosynthesis as a function of this organelle.","method":"Sequence analysis of N-terminal presequences; immunolocalization of ACP (used as representative marker); GFP reporter targeting in transgenic T. gondii","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct immunolocalization was performed for ACP (not FabZ itself), with N-terminal presequence analysis supporting FabZ apicoplast targeting; indirect but from two organisms","pmids":["9770490"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2003,"finding":"FabZ (PF3D7_1323000) was cloned and overexpressed as a 17-kDa recombinant protein that catalyzes the dehydration of beta-hydroxyacyl-ACP to trans-2-acyl-ACP (the third step of the FAS elongation cycle). It has a Km of 199 µM and kcat/Km of 80.4 M⁻¹s⁻¹ for beta-hydroxybutyryl-CoA and utilizes crotonoyl-CoA more efficiently (Km = 86 µM, kcat/Km = 220 M⁻¹s⁻¹). Inhibitors NAS-91 and NAS-21 competitively blocked crotonoyl-CoA binding, inhibited parasite growth in culture, and blocked fatty acid synthesis both in cell-free extracts and in situ.","method":"Recombinant protein overexpression; in vitro enzyme kinetics assay; competitive inhibition kinetics; P. falciparum culture growth inhibition; cell-free extract FAS inhibition assay; homology modeling","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro enzymatic reconstitution with kinetic parameters, mutagenesis-independent but multiple orthogonal methods (kinetics, inhibition, in-situ assay, culture growth); single lab but rigorous","pmids":["12930838"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2003,"finding":"FabZ (PF3D7_1323000) crystals were obtained in orthorhombic space group I222 or I2(1)2(1)2(1) with unit-cell parameters a=71.78, b=81.99, c=97.49 Å, and a complete 2.5 Å dataset was collected, establishing initial crystallographic properties of the enzyme.","method":"Hanging-drop vapour-diffusion and microbatch crystallization; X-ray data collection to 2.5 Å","journal":"Acta crystallographica. Section D, Biological crystallography","confidence":"Low","confidence_rationale":"Tier 3 / Weak — preliminary crystallographic report only, no structure solved or functionally validated in this paper","pmids":["14684903"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2005,"finding":"The crystal structure of FabZ (PF3D7_1323000) was solved by SAD phasing to 2.1 Å resolution. The asymmetric unit contains a hexamer (trimer of dimers), each dimer adopting the 'hot dog' fold. Each dimer contributes to two active sites, which are L-shaped hydrophobic tunnels. Catalytic residues His133 and Glu147' (from the opposing subunit), together with His98', form the only hydrophilic site in the tunnel. Phe169 closes the tunnel inner end. 3-decynoyl-N-acetylcysteamine was found to interact covalently with FabZ, and an elimination-reaction mechanism catalyzed by His133 and Glu147' was proposed and structurally supported.","method":"X-ray crystallography (SAD phasing, 2.1 Å resolution); inhibitor soaking; structural analysis of active site","journal":"Protein science : a publication of the Protein Society","confidence":"High","confidence_rationale":"Tier 1 / Strong — high-resolution crystal structure with catalytic residue identification and covalent inhibitor complex; rigorous structural methods","pmids":["15930004"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2006,"finding":"FabZ (PF3D7_1323000) was found to exist as a homodimer (d-PfFabZ) under certain crystallization conditions, in contrast to the previously reported active hexameric form. In the dimer, the catalytic histidine adopts a different conformation and moves away from the tunnel, associated with a His-Phe cis-trans peptide flip and a Tyr-Pro flip in a nearby loop, distorting the active site and preventing substrate binding. Dynamic light scattering and size exclusion chromatography showed pH-dependent switching from inactive dimers to active hexamers.","method":"X-ray crystallography (2.4 Å resolution); dynamic light scattering; size exclusion chromatography","journal":"FEBS letters","confidence":"High","confidence_rationale":"Tier 1 / Moderate — crystal structure at 2.4 Å combined with two orthogonal biophysical methods (DLS, SEC) demonstrating conformational switching mechanism","pmids":["16643907"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2006,"finding":"Flavonoids inhibit FabZ (PF3D7_1323000) enzymatic activity in vitro. Isoflavonoids showed moderate but selective activity against FabZ (IC50 7–30 µM). More complex flavonoids and C-3 gallic acid esters of catechins were strong inhibitors (IC50 0.2–1.1 µM). Kinetic analysis with luteolin and (-)-catechin gallate revealed FabZ is inhibited competitively by these compounds.","method":"In vitro enzyme inhibition assay; kinetic analysis (competitive inhibition mode determination)","journal":"Journal of medicinal chemistry","confidence":"Medium","confidence_rationale":"Tier 1 / Moderate — in vitro kinetic assays with mode-of-inhibition determination; single lab, multiple compound classes tested","pmids":["16722653"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2007,"finding":"FabZ (PF3D7_1323000) was reconstituted as part of the complete in vitro elongation module of the P. falciparum type II FAS system (together with FabB/F, FabG, and FabI), and the multi-enzyme reaction was analyzed by MALDI-TOF MS. Inhibition of FabZ with NAS-21/91 and (-)-catechin gallate caused accumulation of upstream intermediates, detectable by MS, demonstrating FabZ's functional position in the elongation cycle.","method":"In vitro reconstitution of FAS elongation module; MALDI-TOF MS analysis of acyl-ACP intermediates; inhibitor-mediated intermediate accumulation","journal":"Antimicrobial agents and chemotherapy","confidence":"High","confidence_rationale":"Tier 1 / Strong — multi-enzyme in vitro reconstitution with MS readout and pharmacological inhibition confirming pathway position; multiple orthogonal methods","pmids":["17485508"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2008,"finding":"Targeted knockout of FabZ in Plasmodium yoelii confirmed that FabZ is dispensable for blood stage replication and mosquito stage development, but that FAS II-deficient liver stage parasites fail to form exo-erythrocytic merozoites, establishing FabZ's essential role specifically at the liver-to-blood stage transition.","method":"Targeted gene deletion (knockout) in P. yoelii; parasite life cycle stage phenotyping","journal":"Cellular microbiology","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean genetic KO with defined stage-specific phenotypic readout; corroborated by parallel FabB/F KO and P. falciparum FabI KO results","pmids":["19068099"],"is_preprint":false,"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":2010,"finding":"Steered molecular dynamics (SMD) simulations of FabZ (PF3D7_1323000) inhibitor binding were used to predict and rank inhibitor activity; a newly designed compound's activity against FabZ was predicted computationally and then confirmed experimentally, demonstrating an interaction model for known and novel inhibitors.","method":"Steered molecular dynamics simulations; molecular docking; experimental biological activity confirmation of a predicted inhibitor","journal":"Journal of the American Chemical Society","confidence":"Medium","confidence_rationale":"Tier 1 / Moderate — computational prediction validated by experimental enzyme inhibition; single lab, novel approach confirmed with one new compound","pmids":["20462212"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2011,"finding":"Crystal structures of FabZ (PF3D7_1323000) in complex with four active-site inhibitors were determined, revealing that: (1) inhibitor binding stabilizes the substrate-binding loop; (2) the substrate-binding tunnel has an overall 'U' shape; (3) Phe169 exists in open and closed conformations controlling tunnel length for accommodating longer substrates; (4) inhibitors directly contact the catalytic residues His133 and Glu147'.","method":"X-ray crystallography of inhibitor-bound FabZ complexes (first reported for any FabZ with active-site inhibitors)","journal":"Journal of structural biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structures of four inhibitor complexes providing structural basis for inhibitory mechanism and substrate selectivity; multiple complexes in single study","pmids":["21843645"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"finding":"2-Hexadecynoic acid (2-HDA) inhibits FabZ (PF3D7_1323000) in vitro with an IC50 of 0.58 µg/ml; enzyme kinetics and molecular modeling provided insights into the binding mechanism of 2-HDA on FabZ.","method":"In vitro enzyme inhibition assay; enzyme kinetics; molecular modeling","journal":"Bioorganic & medicinal chemistry","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in vitro kinetics with molecular modeling; single lab, single compound class","pmids":["20855214"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"finding":"A high-yield method for producing acylated P. falciparum ACP (PfACP) substrates was developed and validated for use with FabZ (PF3D7_1323000) and other FAS-II enzymes, confirming that these acyl-ACP species are fully functional substrates for the P. falciparum FAS-II system including FabZ.","method":"Enzymatic acylation of PfACP using E. coli holo-ACP synthase and acyl-ACP synthase; functional validation with FAS-II enzymes","journal":"Biochemistry and biophysics reports","confidence":"Low","confidence_rationale":"Tier 3 / Weak — methodological study confirming substrate functionality; single lab, no deep mechanistic characterization of FabZ itself","pmids":["28955970"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"FabZ (PF3D7_1323000) is the apicoplast-targeted beta-hydroxyacyl-ACP dehydratase of P. falciparum that catalyzes the third step of the type II fatty acid elongation cycle (dehydration of beta-hydroxyacyl-ACP to trans-2-acyl-ACP) via an elimination mechanism mediated by catalytic residues His133 and Glu147'; it functions as an active hexamer (trimer of dimers with 'hot dog' fold) that can switch to an inactive dimer via pH-dependent peptide flips, is competitively inhibited by diverse natural and synthetic compounds, is essential specifically for liver-stage parasite development into exo-erythrocytic merozoites (but dispensable in blood and mosquito stages), and participates in the reconstituted four-enzyme FAS elongation module in vitro."},"narrative":{"mechanistic_narrative":"FabZ (PF3D7_1323000) is the beta-hydroxyacyl-ACP dehydratase of the P. falciparum apicoplast-localized type II fatty acid synthesis (FAS-II) pathway, catalyzing the third step of the elongation cycle—dehydration of beta-hydroxyacyl-ACP to trans-2-acyl-ACP [PMID:9770490, PMID:12930838]. The recombinant 17-kDa enzyme was reconstituted in vitro with defined kinetic parameters and was shown to occupy its expected position in the elongation cycle when assembled with FabB/F, FabG, and FabI into the complete four-enzyme module, where its pharmacological inhibition causes accumulation of upstream acyl-ACP intermediates [PMID:12930838, PMID:17485508]. Structurally, FabZ assembles as a catalytically active hexamer (a trimer of 'hot dog'-fold dimers) whose L-shaped hydrophobic active-site tunnels are formed at dimer interfaces; catalysis proceeds by an elimination mechanism involving His133 and Glu147' from the opposing subunit, with Phe169 gating the tunnel to accommodate substrates of differing acyl-chain length [PMID:15930004, PMID:21843645]. The enzyme undergoes a pH-dependent switch between the active hexamer and an inactive dimer, in which cis-trans peptide flips displace the catalytic histidine and distort the active site [PMID:16643907]. Genetically, FabZ is dispensable in blood and mosquito stages but essential for liver-stage development into exo-erythrocytic merozoites, defining FAS-II as critical specifically at the liver-to-blood transition [PMID:19068099]. FabZ is competitively inhibited at its active site by diverse natural and synthetic compounds, and multiple inhibitor-bound crystal structures show direct contacts with the catalytic residues, making it a structurally well-defined antimalarial target [PMID:12930838, PMID:16722653, PMID:21843645].","teleology":[{"year":1998,"claim":"Establishing where fatty acid biosynthesis occurs answered whether the apicoplast harbors a FAS pathway, placing FabZ in an organellar compartment.","evidence":"N-terminal presequence analysis and ACP immunolocalization as a pathway proxy in P. falciparum, with GFP targeting in T. gondii","pmids":["9770490"],"confidence":"Medium","gaps":["Direct immunolocalization of FabZ protein itself was not performed","Targeting was inferred from presequence and an ACP proxy rather than experimental FabZ import"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2003,"claim":"Recombinant expression and enzymatic assay answered what reaction FabZ catalyzes and confirmed it as the dehydratase of the FAS elongation cycle, while identifying competitive inhibitors active in culture.","evidence":"Recombinant overexpression, in vitro dehydratase kinetics, competitive inhibition by NAS-91/NAS-21, and culture and cell-free FAS growth-inhibition assays in P. falciparum","pmids":["12930838"],"confidence":"High","gaps":["Kinetics measured on CoA surrogate substrates rather than the physiological acyl-ACP","Catalytic residues not yet defined by structure or mutagenesis"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2005,"claim":"Solving the crystal structure answered how FabZ is organized and how it catalyzes dehydration, defining the active hexamer, the hot-dog fold, and the catalytic machinery.","evidence":"SAD-phased 2.1 A crystal structure with 3-decynoyl-N-acetylcysteamine covalent complex and active-site analysis in P. falciparum","pmids":["15930004","14684903"],"confidence":"High","gaps":["Catalytic roles of His133 and Glu147' inferred structurally, not tested by mutagenesis","No structure of a physiological acyl-ACP substrate complex"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2006,"claim":"Discovery of an inactive dimeric form answered how FabZ activity can be regulated, revealing a pH-dependent oligomeric switch coupled to peptide flips at the active site.","evidence":"2.4 A crystal structure of the dimer plus dynamic light scattering and size-exclusion chromatography of oligomeric state in P. falciparum","pmids":["16643907"],"confidence":"High","gaps":["Physiological relevance and trigger of the pH-dependent switch in vivo unknown","Whether oligomeric switching regulates FAS flux in the parasite untested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2007,"claim":"Reconstituting the four-enzyme elongation module answered whether FabZ operates in a functional pathway context and pinpointed its step by inhibitor-induced intermediate accumulation.","evidence":"In vitro reconstitution with FabB/F, FabG, FabI and MALDI-TOF MS of acyl-ACP intermediates under FabZ inhibition in P. falciparum","pmids":["17485508"],"confidence":"High","gaps":["Physiological chain-length preference across the cycle not fully mapped","Regulation of module assembly in vivo not addressed"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2008,"claim":"Genetic knockout answered when FabZ is required during the life cycle, showing FAS-II and FabZ are essential only at the liver-to-blood transition.","evidence":"Targeted gene deletion in P. yoelii with life-cycle stage phenotyping","pmids":["19068099"],"confidence":"High","gaps":["Shown in P. yoelii; direct P. falciparum FabZ knockout not reported here","Molecular basis of the liver-stage-specific requirement not defined"],"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":2011,"claim":"Inhibitor-bound structures and computational modeling answered how diverse inhibitors engage the active site, providing a structural basis for competitive inhibition and substrate accommodation.","evidence":"Crystal structures of four active-site inhibitor complexes plus steered molecular dynamics predictions validated experimentally, and flavonoid/2-HDA kinetic inhibition studies in P. falciparum","pmids":["21843645","20462212","16722653","20855214"],"confidence":"High","gaps":["No inhibitor validated as a stage-specific antimalarial in vivo","Selectivity over host dehydratases not established in these structures"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"claim":"Development of acylated PfACP substrates answered whether physiological acyl-ACP species serve FabZ, enabling assays with native rather than surrogate substrates.","evidence":"Enzymatic acylation of PfACP and functional validation with FAS-II enzymes in P. falciparum","pmids":["28955970"],"confidence":"Low","gaps":["Methodological study without deep mechanistic characterization of FabZ","No new FabZ kinetics on native acyl-ACP reported"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether the pH-dependent hexamer-dimer switch operates as a physiological regulatory mechanism of FAS-II flux in the parasite, and whether FabZ can be selectively drugged to block liver-stage development in vivo, remain unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No in vivo test of oligomeric regulation","No inhibitor demonstrated to block liver-stage transition in an infection model","Catalytic residue assignments not confirmed by mutagenesis"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Homohexamer (trimer of 'hot dog'-fold dimers), catalytically active form [#3]","Inactive homodimer, pH-dependent switch from hexamer [#4]","In vitro-reconstituted FAS-II elongation module with FabB/F, FabG, FabI [#6]"],"partners":["ACYL-ACP / PFACP (SUBSTRATE CARRIER) [#1, #11]","FABB/F, FABG, FABI (CO-RECONSTITUTED FAS-II ELONGATION ENZYMES) [#6]"],"other_free_text":["Catalytic elimination mechanism mediated by His133 and Glu147' from the opposing subunit, with His98' in the hydrophilic active site [#3]","Phe169 gates the substrate tunnel (open/closed conformations) controlling accommodation of longer acyl chains [#9]","Competitively inhibited at the active site by NAS-21/NAS-91, flavonoids/catechin gallates, and 2-hexadecynoic acid [#1, #5, #10]","Essential for liver-stage development to exo-erythrocytic merozoites but dispensable in blood and mosquito stages (P. yoelii knockout) [#7]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"9770490","id":"PMC_9770490","title":"Nuclear-encoded proteins target to the plastid in Toxoplasma gondii and Plasmodium falciparum.","date":"1998","source":"Proceedings of the National Academy of Sciences of the United States of 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biosynthesis acyl carrier proteins.","date":"2009","source":"Molecular bioSystems","url":"https://pubmed.ncbi.nlm.nih.gov/19462023","citation_count":15,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ACP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"24591179","id":"PMC_24591179","title":"Compound prioritization from inverse docking experiment using receptor-centric and ligand-centric methods: a case study on Plasmodium falciparum Fab enzymes.","date":"2014","source":"Journal of molecular recognition : JMR","url":"https://pubmed.ncbi.nlm.nih.gov/24591179","citation_count":13,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["FabZ"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"23727443","id":"PMC_23727443","title":"Recent developments in the antiprotozoal and anticancer activities of the 2-alkynoic fatty acids.","date":"2013","source":"Chemistry and physics of lipids","url":"https://pubmed.ncbi.nlm.nih.gov/23727443","citation_count":10,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfFabZ"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"14684903","id":"PMC_14684903","title":"Crystallization and preliminary crystallographic analysis of beta-hydroxyacyl ACP dehydratase (FabZ) from Plasmodium falciparum.","date":"2003","source":"Acta crystallographica. Section D, Biological crystallography","url":"https://pubmed.ncbi.nlm.nih.gov/14684903","citation_count":8,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["FabZ","beta-hydroxyacyl-ACP dehydratase","ACP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41959251","id":"PMC_41959251","title":"Acyl Carrier Protein is Essential for Apicoplast Biogenesis in Malaria Parasites Independent of Fatty Acid Synthesis.","date":"2026","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/41959251","citation_count":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ACP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41775037","id":"PMC_41775037","title":"TEpiNom: A computational framework integrating population data to prioritize Plasmodium falciparum T cell epitopes.","date":"2026","source":"Vaccine","url":"https://pubmed.ncbi.nlm.nih.gov/41775037","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["FabZ"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"42537022","id":"PMC_42537022","title":"In Silico Exploration of Antimalarial Potential of Ethanolic Leaf Extract of Heliotropium indicum.","date":"2026","source":"Nigerian journal of physiological sciences : official publication of the Physiological Society of Nigeria","url":"https://pubmed.ncbi.nlm.nih.gov/42537022","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["beta-hydroxyacyl-ACP dehydratase","ACP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"40791414","id":"PMC_40791414","title":"Computational Prioritization of T Cell Epitopes to Overcome HLA Restriction and Antigenic Diversity in Plasmodium falciparum.","date":"2025","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/40791414","citation_count":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["FabZ"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"37827299","id":"PMC_37827299","title":"In vitro and in silico anti-malarial activity and cytotoxicity of n-hexyl 1-O-rutinoside (a glycoside) isolated from Annickia polycarpa (DC.) Setten and Maas ex I.M. Turner (Annonaceae).","date":"2023","source":"Journal of ethnopharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/37827299","citation_count":2,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ACP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"28462015","id":"PMC_28462015","title":"Membrane and luminal proteins reach the apicoplast by different trafficking pathways in the malaria parasite Plasmodium falciparum.","date":"2017","source":"PeerJ","url":"https://pubmed.ncbi.nlm.nih.gov/28462015","citation_count":8,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ACP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"28955970","id":"PMC_28955970","title":"A high yield optimized method for the production of acylated ACPs enabling the analysis of enzymes involved in P. falciparum fatty acid biosynthesis.","date":"2016","source":"Biochemistry and biophysics reports","url":"https://pubmed.ncbi.nlm.nih.gov/28955970","citation_count":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ACP","PfACP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25103602","id":"PMC_25103602","title":"2-Octadecynoic acid as a dual life stage inhibitor of Plasmodium infections and plasmodial FAS-II enzymes.","date":"2014","source":"Bioorganic & medicinal chemistry letters","url":"https://pubmed.ncbi.nlm.nih.gov/25103602","citation_count":7,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfFabZ"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":21309,"output_tokens":3711,"usd":0.059796,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":9802,"output_tokens":3683,"usd":0.070542,"stage2_stop_reason":"end_turn"},"total_usd":0.130338,"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\": \"FabZ (PF3D7_1323000) is a nuclear-encoded gene whose protein product bears an N-terminal presequence consistent with apicoplast targeting, and immunolocalization data (using ACP as a proxy for the FAS pathway) indicates that FabZ very probably localizes to the apicoplast of P. falciparum, implicating fatty acid biosynthesis as a function of this organelle.\",\n      \"method\": \"Sequence analysis of N-terminal presequences; immunolocalization of ACP (used as representative marker); GFP reporter targeting in transgenic T. gondii\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct immunolocalization was performed for ACP (not FabZ itself), with N-terminal presequence analysis supporting FabZ apicoplast targeting; indirect but from two organisms\",\n      \"pmids\": [\"9770490\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"FabZ (PF3D7_1323000) was cloned and overexpressed as a 17-kDa recombinant protein that catalyzes the dehydration of beta-hydroxyacyl-ACP to trans-2-acyl-ACP (the third step of the FAS elongation cycle). It has a Km of 199 µM and kcat/Km of 80.4 M⁻¹s⁻¹ for beta-hydroxybutyryl-CoA and utilizes crotonoyl-CoA more efficiently (Km = 86 µM, kcat/Km = 220 M⁻¹s⁻¹). Inhibitors NAS-91 and NAS-21 competitively blocked crotonoyl-CoA binding, inhibited parasite growth in culture, and blocked fatty acid synthesis both in cell-free extracts and in situ.\",\n      \"method\": \"Recombinant protein overexpression; in vitro enzyme kinetics assay; competitive inhibition kinetics; P. falciparum culture growth inhibition; cell-free extract FAS inhibition assay; homology modeling\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro enzymatic reconstitution with kinetic parameters, mutagenesis-independent but multiple orthogonal methods (kinetics, inhibition, in-situ assay, culture growth); single lab but rigorous\",\n      \"pmids\": [\"12930838\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"FabZ (PF3D7_1323000) crystals were obtained in orthorhombic space group I222 or I2(1)2(1)2(1) with unit-cell parameters a=71.78, b=81.99, c=97.49 Å, and a complete 2.5 Å dataset was collected, establishing initial crystallographic properties of the enzyme.\",\n      \"method\": \"Hanging-drop vapour-diffusion and microbatch crystallization; X-ray data collection to 2.5 Å\",\n      \"journal\": \"Acta crystallographica. Section D, Biological crystallography\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — preliminary crystallographic report only, no structure solved or functionally validated in this paper\",\n      \"pmids\": [\"14684903\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"The crystal structure of FabZ (PF3D7_1323000) was solved by SAD phasing to 2.1 Å resolution. The asymmetric unit contains a hexamer (trimer of dimers), each dimer adopting the 'hot dog' fold. Each dimer contributes to two active sites, which are L-shaped hydrophobic tunnels. Catalytic residues His133 and Glu147' (from the opposing subunit), together with His98', form the only hydrophilic site in the tunnel. Phe169 closes the tunnel inner end. 3-decynoyl-N-acetylcysteamine was found to interact covalently with FabZ, and an elimination-reaction mechanism catalyzed by His133 and Glu147' was proposed and structurally supported.\",\n      \"method\": \"X-ray crystallography (SAD phasing, 2.1 Å resolution); inhibitor soaking; structural analysis of active site\",\n      \"journal\": \"Protein science : a publication of the Protein Society\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — high-resolution crystal structure with catalytic residue identification and covalent inhibitor complex; rigorous structural methods\",\n      \"pmids\": [\"15930004\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"FabZ (PF3D7_1323000) was found to exist as a homodimer (d-PfFabZ) under certain crystallization conditions, in contrast to the previously reported active hexameric form. In the dimer, the catalytic histidine adopts a different conformation and moves away from the tunnel, associated with a His-Phe cis-trans peptide flip and a Tyr-Pro flip in a nearby loop, distorting the active site and preventing substrate binding. Dynamic light scattering and size exclusion chromatography showed pH-dependent switching from inactive dimers to active hexamers.\",\n      \"method\": \"X-ray crystallography (2.4 Å resolution); dynamic light scattering; size exclusion chromatography\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — crystal structure at 2.4 Å combined with two orthogonal biophysical methods (DLS, SEC) demonstrating conformational switching mechanism\",\n      \"pmids\": [\"16643907\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"Flavonoids inhibit FabZ (PF3D7_1323000) enzymatic activity in vitro. Isoflavonoids showed moderate but selective activity against FabZ (IC50 7–30 µM). More complex flavonoids and C-3 gallic acid esters of catechins were strong inhibitors (IC50 0.2–1.1 µM). Kinetic analysis with luteolin and (-)-catechin gallate revealed FabZ is inhibited competitively by these compounds.\",\n      \"method\": \"In vitro enzyme inhibition assay; kinetic analysis (competitive inhibition mode determination)\",\n      \"journal\": \"Journal of medicinal chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro kinetic assays with mode-of-inhibition determination; single lab, multiple compound classes tested\",\n      \"pmids\": [\"16722653\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"FabZ (PF3D7_1323000) was reconstituted as part of the complete in vitro elongation module of the P. falciparum type II FAS system (together with FabB/F, FabG, and FabI), and the multi-enzyme reaction was analyzed by MALDI-TOF MS. Inhibition of FabZ with NAS-21/91 and (-)-catechin gallate caused accumulation of upstream intermediates, detectable by MS, demonstrating FabZ's functional position in the elongation cycle.\",\n      \"method\": \"In vitro reconstitution of FAS elongation module; MALDI-TOF MS analysis of acyl-ACP intermediates; inhibitor-mediated intermediate accumulation\",\n      \"journal\": \"Antimicrobial agents and chemotherapy\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — multi-enzyme in vitro reconstitution with MS readout and pharmacological inhibition confirming pathway position; multiple orthogonal methods\",\n      \"pmids\": [\"17485508\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"Targeted knockout of FabZ in Plasmodium yoelii confirmed that FabZ is dispensable for blood stage replication and mosquito stage development, but that FAS II-deficient liver stage parasites fail to form exo-erythrocytic merozoites, establishing FabZ's essential role specifically at the liver-to-blood stage transition.\",\n      \"method\": \"Targeted gene deletion (knockout) in P. yoelii; parasite life cycle stage phenotyping\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean genetic KO with defined stage-specific phenotypic readout; corroborated by parallel FabB/F KO and P. falciparum FabI KO results\",\n      \"pmids\": [\"19068099\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Steered molecular dynamics (SMD) simulations of FabZ (PF3D7_1323000) inhibitor binding were used to predict and rank inhibitor activity; a newly designed compound's activity against FabZ was predicted computationally and then confirmed experimentally, demonstrating an interaction model for known and novel inhibitors.\",\n      \"method\": \"Steered molecular dynamics simulations; molecular docking; experimental biological activity confirmation of a predicted inhibitor\",\n      \"journal\": \"Journal of the American Chemical Society\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — computational prediction validated by experimental enzyme inhibition; single lab, novel approach confirmed with one new compound\",\n      \"pmids\": [\"20462212\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Crystal structures of FabZ (PF3D7_1323000) in complex with four active-site inhibitors were determined, revealing that: (1) inhibitor binding stabilizes the substrate-binding loop; (2) the substrate-binding tunnel has an overall 'U' shape; (3) Phe169 exists in open and closed conformations controlling tunnel length for accommodating longer substrates; (4) inhibitors directly contact the catalytic residues His133 and Glu147'.\",\n      \"method\": \"X-ray crystallography of inhibitor-bound FabZ complexes (first reported for any FabZ with active-site inhibitors)\",\n      \"journal\": \"Journal of structural biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structures of four inhibitor complexes providing structural basis for inhibitory mechanism and substrate selectivity; multiple complexes in single study\",\n      \"pmids\": [\"21843645\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"2-Hexadecynoic acid (2-HDA) inhibits FabZ (PF3D7_1323000) in vitro with an IC50 of 0.58 µg/ml; enzyme kinetics and molecular modeling provided insights into the binding mechanism of 2-HDA on FabZ.\",\n      \"method\": \"In vitro enzyme inhibition assay; enzyme kinetics; molecular modeling\",\n      \"journal\": \"Bioorganic & medicinal chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro kinetics with molecular modeling; single lab, single compound class\",\n      \"pmids\": [\"20855214\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"A high-yield method for producing acylated P. falciparum ACP (PfACP) substrates was developed and validated for use with FabZ (PF3D7_1323000) and other FAS-II enzymes, confirming that these acyl-ACP species are fully functional substrates for the P. falciparum FAS-II system including FabZ.\",\n      \"method\": \"Enzymatic acylation of PfACP using E. coli holo-ACP synthase and acyl-ACP synthase; functional validation with FAS-II enzymes\",\n      \"journal\": \"Biochemistry and biophysics reports\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — methodological study confirming substrate functionality; single lab, no deep mechanistic characterization of FabZ itself\",\n      \"pmids\": [\"28955970\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"FabZ (PF3D7_1323000) is the apicoplast-targeted beta-hydroxyacyl-ACP dehydratase of P. falciparum that catalyzes the third step of the type II fatty acid elongation cycle (dehydration of beta-hydroxyacyl-ACP to trans-2-acyl-ACP) via an elimination mechanism mediated by catalytic residues His133 and Glu147'; it functions as an active hexamer (trimer of dimers with 'hot dog' fold) that can switch to an inactive dimer via pH-dependent peptide flips, is competitively inhibited by diverse natural and synthetic compounds, is essential specifically for liver-stage parasite development into exo-erythrocytic merozoites (but dispensable in blood and mosquito stages), and participates in the reconstituted four-enzyme FAS elongation module in vitro.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"FabZ (PF3D7_1323000) is the beta-hydroxyacyl-ACP dehydratase of the P. falciparum apicoplast-localized type II fatty acid synthesis (FAS-II) pathway, catalyzing the third step of the elongation cycle—dehydration of beta-hydroxyacyl-ACP to trans-2-acyl-ACP [#0, #1]. The recombinant 17-kDa enzyme was reconstituted in vitro with defined kinetic parameters and was shown to occupy its expected position in the elongation cycle when assembled with FabB/F, FabG, and FabI into the complete four-enzyme module, where its pharmacological inhibition causes accumulation of upstream acyl-ACP intermediates [#1, #6]. Structurally, FabZ assembles as a catalytically active hexamer (a trimer of 'hot dog'-fold dimers) whose L-shaped hydrophobic active-site tunnels are formed at dimer interfaces; catalysis proceeds by an elimination mechanism involving His133 and Glu147' from the opposing subunit, with Phe169 gating the tunnel to accommodate substrates of differing acyl-chain length [#3, #9]. The enzyme undergoes a pH-dependent switch between the active hexamer and an inactive dimer, in which cis-trans peptide flips displace the catalytic histidine and distort the active site [#4]. Genetically, FabZ is dispensable in blood and mosquito stages but essential for liver-stage development into exo-erythrocytic merozoites, defining FAS-II as critical specifically at the liver-to-blood transition [#7]. FabZ is competitively inhibited at its active site by diverse natural and synthetic compounds, and multiple inhibitor-bound crystal structures show direct contacts with the catalytic residues, making it a structurally well-defined antimalarial target [#1, #5, #9].\",\n  \"teleology\": [\n    {\n      \"year\": 1998,\n      \"claim\": \"Establishing where fatty acid biosynthesis occurs answered whether the apicoplast harbors a FAS pathway, placing FabZ in an organellar compartment.\",\n      \"evidence\": \"N-terminal presequence analysis and ACP immunolocalization as a pathway proxy in P. falciparum, with GFP targeting in T. gondii\",\n      \"pmids\": [\"9770490\"],\n      \"confidence\": \"Medium\",\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}],\n      \"gaps\": [\"Direct immunolocalization of FabZ protein itself was not performed\", \"Targeting was inferred from presequence and an ACP proxy rather than experimental FabZ import\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Recombinant expression and enzymatic assay answered what reaction FabZ catalyzes and confirmed it as the dehydratase of the FAS elongation cycle, while identifying competitive inhibitors active in culture.\",\n      \"evidence\": \"Recombinant overexpression, in vitro dehydratase kinetics, competitive inhibition by NAS-91/NAS-21, and culture and cell-free FAS growth-inhibition assays in P. falciparum\",\n      \"pmids\": [\"12930838\"],\n      \"confidence\": \"High\",\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}],\n      \"gaps\": [\"Kinetics measured on CoA surrogate substrates rather than the physiological acyl-ACP\", \"Catalytic residues not yet defined by structure or mutagenesis\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Solving the crystal structure answered how FabZ is organized and how it catalyzes dehydration, defining the active hexamer, the hot-dog fold, and the catalytic machinery.\",\n      \"evidence\": \"SAD-phased 2.1 A crystal structure with 3-decynoyl-N-acetylcysteamine covalent complex and active-site analysis in P. falciparum\",\n      \"pmids\": [\"15930004\", \"14684903\"],\n      \"confidence\": \"High\",\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}],\n      \"gaps\": [\"Catalytic roles of His133 and Glu147' inferred structurally, not tested by mutagenesis\", \"No structure of a physiological acyl-ACP substrate complex\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Discovery of an inactive dimeric form answered how FabZ activity can be regulated, revealing a pH-dependent oligomeric switch coupled to peptide flips at the active site.\",\n      \"evidence\": \"2.4 A crystal structure of the dimer plus dynamic light scattering and size-exclusion chromatography of oligomeric state in P. falciparum\",\n      \"pmids\": [\"16643907\"],\n      \"confidence\": \"High\",\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}],\n      \"gaps\": [\"Physiological relevance and trigger of the pH-dependent switch in vivo unknown\", \"Whether oligomeric switching regulates FAS flux in the parasite untested\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Reconstituting the four-enzyme elongation module answered whether FabZ operates in a functional pathway context and pinpointed its step by inhibitor-induced intermediate accumulation.\",\n      \"evidence\": \"In vitro reconstitution with FabB/F, FabG, FabI and MALDI-TOF MS of acyl-ACP intermediates under FabZ inhibition in P. falciparum\",\n      \"pmids\": [\"17485508\"],\n      \"confidence\": \"High\",\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}],\n      \"gaps\": [\"Physiological chain-length preference across the cycle not fully mapped\", \"Regulation of module assembly in vivo not addressed\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Genetic knockout answered when FabZ is required during the life cycle, showing FAS-II and FabZ are essential only at the liver-to-blood transition.\",\n      \"evidence\": \"Targeted gene deletion in P. yoelii with life-cycle stage phenotyping\",\n      \"pmids\": [\"19068099\"],\n      \"confidence\": \"High\",\n      \"attribution\": [{\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}],\n      \"gaps\": [\"Shown in P. yoelii; direct P. falciparum FabZ knockout not reported here\", \"Molecular basis of the liver-stage-specific requirement not defined\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Inhibitor-bound structures and computational modeling answered how diverse inhibitors engage the active site, providing a structural basis for competitive inhibition and substrate accommodation.\",\n      \"evidence\": \"Crystal structures of four active-site inhibitor complexes plus steered molecular dynamics predictions validated experimentally, and flavonoid/2-HDA kinetic inhibition studies in P. falciparum\",\n      \"pmids\": [\"21843645\", \"20462212\", \"16722653\", \"20855214\"],\n      \"confidence\": \"High\",\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}],\n      \"gaps\": [\"No inhibitor validated as a stage-specific antimalarial in vivo\", \"Selectivity over host dehydratases not established in these structures\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Development of acylated PfACP substrates answered whether physiological acyl-ACP species serve FabZ, enabling assays with native rather than surrogate substrates.\",\n      \"evidence\": \"Enzymatic acylation of PfACP and functional validation with FAS-II enzymes in P. falciparum\",\n      \"pmids\": [\"28955970\"],\n      \"confidence\": \"Low\",\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}],\n      \"gaps\": [\"Methodological study without deep mechanistic characterization of FabZ\", \"No new FabZ kinetics on native acyl-ACP reported\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether the pH-dependent hexamer-dimer switch operates as a physiological regulatory mechanism of FAS-II flux in the parasite, and whether FabZ can be selectively drugged to block liver-stage development in vivo, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"attribution\": [],\n      \"gaps\": [\"No in vivo test of oligomeric regulation\", \"No inhibitor demonstrated to block liver-stage transition in an infection model\", \"Catalytic residue assignments not confirmed by mutagenesis\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0019171\", \"supporting_discovery_ids\": [1, 3, 6]},\n      {\"term_id\": \"GO:0016836\", \"supporting_discovery_ids\": [1, 3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0020011\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006633\", \"supporting_discovery_ids\": [1, 6, 7]},\n      {\"term_id\": \"GO:0009245\", \"supporting_discovery_ids\": [6]}\n    ],\n    \"complexes\": [\n      \"Homohexamer (trimer of 'hot dog'-fold dimers), catalytically active form [#3]\",\n      \"Inactive homodimer, pH-dependent switch from hexamer [#4]\",\n      \"In vitro-reconstituted FAS-II elongation module with FabB/F, FabG, FabI [#6]\"\n    ],\n    \"partners\": [\n      \"Acyl-ACP / PfACP (substrate carrier) [#1, #11]\",\n      \"FabB/F, FabG, FabI (co-reconstituted FAS-II elongation enzymes) [#6]\"\n    ],\n    \"other_free_text\": [\n      \"Catalytic elimination mechanism mediated by His133 and Glu147' from the opposing subunit, with His98' in the hydrophilic active site [#3]\",\n      \"Phe169 gates the substrate tunnel (open/closed conformations) controlling accommodation of longer acyl chains [#9]\",\n      \"Competitively inhibited at the active site by NAS-21/NAS-91, flavonoids/catechin gallates, and 2-hexadecynoic acid [#1, #5, #10]\",\n      \"Essential for liver-stage development to exo-erythrocytic merozoites but dispensable in blood and mosquito stages (P. yoelii knockout) [#7]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1323000","name":null,"product":"beta-hydroxyacyl-ACP dehydratase","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1338200","name":null,"product":"beta-hydroxyacyl-ACP dehydratase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1205800","name":null,"product":"beta-hydroxyacyl-ACP dehydratase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"FabZ","evaluation":null}