Affinage · Plasmodium

HSP90

PF3D7_0708400 · heat shock protein 90

Annotated
2026-09-08
90 papers in source corpus 26 papers cited in narrative 26 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PfHsp90 (PF3D7_0708400) is an essential cytosolic molecular chaperone of Plasmodium falciparum that drives intraerythrocytic development, with geldanamycin inhibition arresting the Ring-to-trophozoite transition (PMID:12584193, PMID:15339915). It assembles into ~300 kDa, 11S hetero-oligomeric multi-chaperone complexes containing PfHsp70, the TPR-phosphatase PfPP5, and tubulin, whose integrity is required for heat-shock-dependent cytoprotection and developmental progression (PMID:12584193, PMID:15339915, PMID:11737864). As an elongated, C-terminally dimerizing ATPase, PfHsp90 possesses the highest ATPase activity of any known Hsp90 ortholog, and its cycle is tuned by a suite of co-chaperones — the p23 orthologue Pfp23 suppresses ATPase activity while PfAha1 stimulates it, with the two competing for binding, and the TPR co-chaperones PfHop, PfFKBP35, and PfPP5 docking onto the C-terminal MEEVD motif (PMID:20837488, PMID:22005844, PMID:20140477, PMID:22100910, PMID:19691130, PMID:32679196). Complex assembly is further modulated by an acetylation site overlapping the Aha1/p23 interface (PMID:20837488). Beyond canonical client folding — where it stabilizes calcineurin, chaperones the active 26S proteasome, and interacts with the drug-resistance transporter PfCRT (PMID:15811524, PMID:24098696, PMID:38492573) — PfHsp90 has a nuclear function as a transcriptional repressor, occupying the PfSIR2A/B promoters and recruiting H3K9me3 to enforce heterochromatin (PMID:33538363), while its own febrile-temperature induction is driven by the PfAP2-HS transcription factor (PMID:34400833). Surface HSP90 on female gametes is required for fertilization in the mosquito stage (PMID:38131664). Its N-terminal ATP-binding pocket carries a Plasmodium-specific structural extension that confers pharmacological divergence from human Hsp90 and enables species-selective inhibitors, and a cryptic C-terminal nucleotide-binding site provides a second druggable pocket (PMID:20635416, PMID:24580531, PMID:42406593, PMID:40907219).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2001 Medium

    Establishing that PfHsp90 physically associates with a parasite TPR phosphatase addressed whether the chaperone recruits regulatory partners in P. falciparum.

    Evidence Co-immunoprecipitation of native PfPP5 with PfHsp90 from parasite extract

    PMID:11737864

    Open questions at the time
    • Single co-IP without reciprocal validation
    • Functional consequence of the PfPP5-PfHsp90 interaction not defined
  2. 2003 High

    The unknown essentiality and complex context of PfHsp90 was resolved by showing it forms ~300 kDa Hsp70-containing complexes and that its inhibition arrests development, establishing it as a bona fide drug target.

    Evidence Sedimentation/SEC complex analysis, geldanamycin growth inhibition, and phosphorylation assays; recombinant ATP-binding and GA-inhibition assays

    PMID:12584193 PMID:14514358

    Open questions at the time
    • Stage-specific mechanism of the Ring-to-trophozoite arrest not defined
    • Full complex composition not yet enumerated
  3. 2005 Medium

    Defining the composition and clientele of the PfHsp90 complex addressed which parasite factors depend on the chaperone, expanding it from PfHsp70/PfPP5/tubulin to FKBP35 and calcineurin.

    Evidence Co-immunoprecipitation and GA/CsA pharmacological dissection plus GA-ascomycin synergy in cultured parasites

    PMID:15339915 PMID:15811524 PMID:15850699

    Open questions at the time
    • Direct vs. indirect binding of calcineurin not distinguished
    • Client-folding mechanism not reconstituted
  4. 2010 High

    Biochemical and structural reconstitution answered how PfHsp90's catalytic cycle is regulated, revealing record-high ATPase activity, acetylation-dependent assembly, and a solved N-terminal drug-binding pocket.

    Evidence In vitro ATPase assays, mass spectrometry of PTM sites, HDAC inhibitor complex analysis, Pfp23 ATPase-suppression mutagenesis, and X-ray crystallography of the NTD

    PMID:20140477 PMID:20635416 PMID:20837488

    Open questions at the time
    • Physiological trigger for acetylation in vivo unknown
    • Full-length conformational cycle not captured crystallographically
  5. 2011 High

    Mapping the co-chaperone interfaces resolved how the ATPase cycle is bidirectionally controlled, showing PfAha1 stimulates and Pfp23 suppresses activity while PfHop and PfFKBP35 bridge to PfHsp70 via the MEEVD motif.

    Evidence Split-ubiquitin, GST pull-down, ATPase assays, interface mutagenesis, gel filtration/co-IP, and crystallography plus SPR/NMR of the FKBP35 TPR-MEEVD interaction

    PMID:19691130 PMID:22005844 PMID:22100910

    Open questions at the time
    • Temporal ordering of co-chaperone exchange on the cycle not resolved
    • In vivo stoichiometry of the assembled complex unknown
  6. 2014 Medium

    The question of whether PfHsp90 can be selectively targeted over human Hsp90 was addressed by identifying a Plasmodium-specific structural/dynamic extension in the ATP pocket and linker that confers pharmacological divergence.

    Evidence Yeast complementation drug-sensitivity comparisons, chimeric-linker biophysics, SPR-mapped residue Arg98 for harmine selectivity, and 7-azaindole selective binding studies

    PMID:19320098 PMID:22315411 PMID:22615284 PMID:24580531

    Open questions at the time
    • Selectivity demonstrated largely in surrogate/recombinant systems
    • In-parasite efficacy of selective scaffolds not established here
  7. 2019 Medium

    Solution biophysics and life-cycle profiling extended the mechanistic picture by defining PfHsp90 as a C-terminally dimerizing, elongated homodimer with state-dependent nucleotide thermodynamics and roles beyond blood stage.

    Evidence SAXS, SEC, ITC of ADP vs ATP binding, and liver/blood-stage inhibitor killing with time-course and combination studies

    PMID:29339390 PMID:30797004 PMID:32679196

    Open questions at the time
    • Liver-stage role inferred pharmacologically, not genetically validated
    • Client repertoire in liver stage undefined
  8. 2021 High

    Discovery of nuclear and transcriptional functions redefined PfHsp90 beyond cytosolic folding, showing it both is induced by PfAP2-HS at fever temperatures and itself represses PfSIR2A/B via H3K9me3-directed heterochromatin.

    Evidence PfAP2-HS knockout with ChIP and heat-shock survival assays; ChIP of PfHsp90 and H3K9me3 at SIR2 promoters with inhibitor-reversal transcriptional analysis

    PMID:33538363 PMID:34400833

    Open questions at the time
    • Mechanism recruiting PfHsp90 to specific promoters unknown
    • Link between chaperone activity and repressor function not established
  9. 2023 Medium

    Identifying surface HSP90 on female gametes addressed whether the chaperone has a role in transmission, showing it is required for fertilization in the mosquito.

    Evidence Phage peptide display, antibody binding, and fertilization-inhibition/peptide-competition assays

    PMID:38131664

    Open questions at the time
    • Mechanism by which a cytosolic chaperone reaches the gamete surface unresolved
    • Fertilization partner/receptor on the gamete surface unknown
  10. 2024 High

    Unbiased target-engagement profiling identified the 26S proteasome as a PfHsp90 client, establishing that the chaperone directly sustains proteasomal hydrolytic activity.

    Evidence Thermal proteome profiling under selective inhibition with biochemical proteasome-activity and cellular validation

    PMID:38492573

    Open questions at the time
    • Which proteasome subunit(s) PfHsp90 engages not defined
    • Structural basis of proteasome chaperoning unknown
  11. 2026 High

    Resistance selection and a newly mapped cryptic C-terminal site clarified the druggable landscape, showing distinct binding-pocket mutation profiles for geldanamycin versus AUY-922 and a second nucleotide-binding pocket.

    Evidence In vitro drug selection with whole-genome sequencing, conditional knockdown, binding-affinity and yeast complementation; ATP-resin/lysine-reactive probe labeling, limited proteolysis, and mutagenesis of the C-terminal site

    PMID:40907219 PMID:42406593

    Open questions at the time
    • Physiological function of the cryptic C-terminal nucleotide site unknown
    • Mechanism of the A41S resistance paradox not fully resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PfHsp90's cytosolic chaperone cycle is coordinated with its distinct nuclear-repressor, gamete-surface, and proteasome-chaperoning roles, and how its clientele shifts across life-cycle stages, remains unresolved.
  • No unified model linking chaperone ATPase cycle to transcriptional repression
  • Stage-specific client repertoire not mapped
  • Trafficking to gamete surface unexplained

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Partners
26S PROTEASOMEPFAHA1PFCRTPFFKBP35PFHOPPFHSP70PFP23PFPP5PLASMODIAL CALCINEURIN (PFCN)TUBULIN
Complex memberships
PfHsp90-PfHop-PfHsp70 ternary complexPfHsp90-active 26S proteasome complex~300 kDa / 11S PfHsp90 multi-chaperone complex containing PfHsp70, PfPP5, and tubulin

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 PfHsp90 exists in ~300 kDa, 11S complexes in P. falciparum that contain PfHsp70; geldanamycin (GA) inhibits parasite growth by arresting Ring-to-trophozoite transition, selectively inhibits PfHsp90 phosphorylation, and disrupts the PfHsp90 multi-chaperone complex, establishing PfHsp90 as essential for intraerythrocytic development. Sedimentation analysis, size exclusion chromatography, homology modeling of GA-binding pocket, drug inhibition assays, metabolic labeling/phosphorylation analysis, flow cytometry The Journal of biological chemistry High 12584193
2003 Recombinant PfHsp90 binds ATP in vitro, and this ATP-binding activity is specifically inhibited by geldanamycin; PfHsp90 mRNA is predominantly expressed in ring and trophozoite stages while the protein is present in all asexual blood stages. Recombinant protein expression, ATP-binding assay, drug inhibition assay, stage-specific protein/mRNA analysis Malaria journal Medium 14514358
2004 The PfHsp90 multi-chaperone complex, which includes PfHsp70, PfPP5, and tubulin, mediates heat shock-dependent cytoprotection and promotes Ring-to-trophozoite progression; GA disrupts this complex and blocks temperature-dependent developmental promotion. Flow cytometry, geldanamycin-based complex disruption, co-immunoprecipitation/complex isolation The Journal of biological chemistry Medium 15339915
2001 PfPP5 (a tetratricopeptide repeat serine/threonine phosphatase) co-immunoprecipitates with PfHsp90 in P. falciparum, establishing a direct interaction between these two proteins in the parasite. Co-immunoprecipitation of native proteins BMC microbiology Medium 11737864
2005 PfFKBP35 associates with PfHsp90 via its TPR domain in vivo; geldanamycin and ascomycin (a FK506 derivative) act synergistically to inhibit P. falciparum erythrocytic growth, consistent with functional coupling of FKBP35 and Hsp90. Co-immunoprecipitation, drug synergy assay in cultured parasites Molecular and biochemical parasitology Medium 15850699
2005 Plasmodial calcineurin (PfCN) associates with PfHsp90 in vivo; GA disrupts this PfHsp90–calcineurin association but cyclosporin A does not, demonstrating that PfHsp90 is required for stabilizing the calcineurin complex in the parasite. Co-immunoprecipitation with native parasite extracts, GA and CsA treatment Molecular and biochemical parasitology Medium 15811524
2010 Full-length recombinant PfHsp90 exhibits the highest ATPase activity among known Hsp90 orthologs (6-fold higher than human Hsp90); GA inhibits PfHsp90 ATPase activity more robustly than human Hsp90. Mass spectrometry identified an acetylation site on PfHsp90 that overlaps with the Aha1 and p23 co-chaperone binding domain; treatment with a histone deacetylase inhibitor partially dissociates the PfHsp90 complex, suggesting acetylation modulates multichaperone assembly. In vitro ATPase assay with purified recombinant protein, mass spectrometry, HDAC inhibitor treatment and complex analysis The Journal of biological chemistry High 20837488
2010 Crystal structure of the N-terminal ATP-binding domain of PfHsp90 was solved in apo and ADP-bound states at 2.3 Å resolution, revealing high structural similarity to human Hsp90 in the drug-binding pocket and confirming the same mode of geldanamycin binding. X-ray crystallography Proteins High 20635416
2009 PfHsp90 expressed in yeast (replacing endogenous yeast Hsp90) confers differential sensitivity to geldanamycin vs. radicicol relative to human Hsp90, demonstrating intrinsic pharmacological differences between PfHsp90 and its human ortholog in a living cellular context. Yeast complementation assay with isogenic strains, drug sensitivity comparison Molecular and biochemical parasitology Medium 19320098
2011 PfHop co-localizes with PfHsp70 and PfHsp90 in trophozoite-stage parasites and forms a complex with both chaperones as demonstrated by gel filtration and co-immunoprecipitation, suggesting PfHop mediates the functional interaction between PfHsp70 and PfHsp90. Immunofluorescence microscopy (co-localization), gel filtration chromatography, co-immunoprecipitation Cell stress & chaperones Medium 22005844
2010 Recombinant Pfp23 (P. falciparum p23 co-chaperone) directly interacts with PfHsp90 and suppresses its ATPase activity; site-directed mutagenesis identified residues K91, H93, W94, and K96 in Pfp23 as critical for PfHsp90 binding. In vitro ATPase assay, recombinant protein interaction studies, site-directed mutagenesis, citrate synthase aggregation suppression assay Cellular and molecular life sciences High 20140477
2011 PfAha1 (P. falciparum Aha1 co-chaperone) interacts with PfHsp90 in an ATP- and MgCl2-dependent manner, as established by split-ubiquitin assay and GST pull-down; the interaction is competed by Pfp23. Residue N108 of PfAha1 is essential for PfHsp90 binding by site-directed mutagenesis. PfAha1 stimulates PfHsp90 ATPase activity. Split-ubiquitin yeast assay, GST pull-down, site-directed mutagenesis, ATPase activity assay The international journal of biochemistry & cell biology High 22100910
2009 The TPR domain of PfFKBP35 was crystallized and its interaction with the PfHsp90 C-terminal MEEVD pentapeptide was demonstrated by surface plasmon resonance and NMR; mutagenesis of conserved carboxylate-clamp residues abolished Hsp90 MEEVD binding, establishing the molecular basis of PfFKBP35–PfHsp90 interaction. X-ray crystallography, surface plasmon resonance, NMR spectroscopy, site-directed mutagenesis Protein science High 19691130
2012 Introducing the human or P. falciparum charged linker sequences into yeast Hsp90 showed that linker sequence (not just length) modulates ATPase activity, cochaperone interaction, and conformation, establishing that the extended charged linker unique to PfHsp90 is functionally significant. Chimeric Hsp90 construction in yeast, in vitro ATPase assay, biophysical characterization Proceedings of the National Academy of Sciences Medium 22315411
2012 Site-directed mutagenesis of Arg98 in PfHsp90 abolished selective binding of the harmine alkaloid, identifying Arg98 as critical for the species-selective binding of harmine to PfHsp90's ATP-binding domain. Site-directed mutagenesis, surface plasmon resonance Antimicrobial agents and chemotherapy Medium 22615284
2014 The ATP-binding pocket of PfHsp90 has a Plasmodium-specific structural extension that differs in tertiary structure and dynamics (not sequence) from human Hsp90; exploiting this dynamic difference enabled discovery of 7-azaindole compounds that exclusively bind recombinant PfHsp90 N-terminal domain but not human Hsp90, and preferentially inhibit yeast complemented with PfHsp90. Structural/dynamics analysis, in vitro binding assays with recombinant domains, yeast complementation growth assay Journal of medicinal chemistry Medium 24580531
2013 LC-MS/MS of PfHsp90 interactors identified the P. falciparum chloroquine resistance transporter (PfCRT) as a direct or indirect interactor of PfHsp90; the PfHsp90 inhibitor PU-H71 synergizes with chloroquine in vitro and in the P. berghei mouse model, suggesting PfHsp90 chaperones PfCRT. LC-MS/MS interactomics of PfHsp90 pulldown, surface plasmon resonance (PU-H71 affinity), ATPase assay, in vitro drug synergy, P. berghei mouse model PloS one Medium 24098696
2019 PfHsp90 inhibition (by SNX-0723 and other inhibitors) kills P. falciparum at both liver and blood stages; expression analysis and time-course inhibition studies support a role for PfHsp90 in late liver-stage parasite development. PfHsp90 inhibitor SNX-0723 combined with PIK-75 synergistically reduces liver-stage parasite load. Cell-based liver- and blood-stage parasite assays, time-course inhibition, expression analysis, drug combination studies Antimicrobial agents and chemotherapy Medium 29339390
2021 PfAP2-HS transcription factor activates transcription of hsp90 (and hsp70-1) at elevated febrile temperatures; parasites lacking PfAP2-HS show reduced heat-shock survival and severe growth defects, establishing that hsp90 upregulation at fever temperatures is under PfAP2-HS control. Conditional/engineered gene knockout, transcriptional analysis, ChIP (promoter binding), heat-shock survival assay Nature microbiology High 34400833
2021 PfHsp90 acts as a transcriptional repressor of PfSIR2A and PfSIR2B by occupying their promoter-proximal regions and recruiting H3K9me3, inducing a heterochromatic state; this repression is reversed by GA or radicicol (PfHsp90 inhibitors), leading to de-repression of var genes at sub-telomeric regions. ChIP (chromatin immunoprecipitation for PfHsp90 at promoters and H3K9me3), drug treatment with PfHsp90 inhibitors, transcriptional analysis Molecular microbiology Medium 33538363
2024 Thermal proteome profiling following selective PfHsp90 inhibition (using Tropane 1 and XL888 derivatives) identified the 26S proteasome as enriched among proteins with perturbed stability; biochemical and cellular studies showed that PfHsp90 directly promotes proteasome hydrolytic activity by chaperoning the active 26S complex. Thermal proteome profiling, biochemical proteasome activity assays, cellular imaging/analysis, selective PfHsp90 inhibitor treatment Cell chemical biology High 38492573
2023 HSP90 is present on the surface of Plasmodium female gametes; anti-Hsp90 antibodies inhibit fertilization, and peptide competition experiments established that female gamete surface HSP90 is required for gamete fertilization in the mosquito. Phage peptide display screening, antibody binding assays, fertilization inhibition assay mBio Medium 38131664
2019 Recombinant PfHsp90 behaves as an elongated, flexible homodimer in solution (sub-micromolar dissociation constant); its C-terminal domain is required for dimerization. PfHsp90 and PfHsp90NMD interact with adenosine nucleotides via the NTD, and Mg2+ is critical for strong nucleotide binding. Small-angle X-ray scattering (SAXS), size exclusion chromatography, isothermal titration calorimetry Archives of biochemistry and biophysics Medium 32679196
2019 Isothermal titration calorimetry showed that PfHsp90 has distinct thermodynamic signatures for ADP vs. ATP binding: ADP interaction is enthalpy-driven but entropy-opposed, while ATP interaction is driven by both enthalpy and entropy, indicating state-dependent conformational properties of PfHsp90. Isothermal titration calorimetry, comparative thermodynamic analysis International journal of biological macromolecules Medium 30797004
2026 In vitro selection experiments identified 10 distinct resistance mutations to geldanamycin in PfHsp90 conferring up to 22-fold resistance; AUY-922 (binding same ATP site) yielded only one mutation (A41S) with 2-fold resistance. The A41S mutation paradoxically increased AUY-922 binding affinity via additional hydrogen bonding yet conferred resistance; conditional PfHsp90 knockdown increased geldanamycin sensitivity but not AUY-922 activity, suggesting different target dependencies. In vitro drug selection, whole-genome sequencing of resistant parasites, conditional knockdown, binding affinity measurement, yeast complementation Cell reports High 42406593
2025 In vitro experiments demonstrated that PfHsp90 has a cryptic C-terminal nucleotide-binding site: an ATP-reactive lysine-reactive probe and an ATP resin specifically interacted with PfHsp90 C-terminal truncation; limited proteolysis showed association with ATP, dATP, and ADP but not AMP or GTP; mutagenesis defined molecular determinants of this interaction. Affinity chromatography (ATP resin), lysine-reactive nucleotide analog labeling, limited proteolysis, site-directed mutagenesis, in silico analysis Bioorganic & medicinal chemistry Medium 40907219

Source papers

Stage 0 corpus · 90 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Heat shock protein 90 function is essential for Plasmodium falciparum growth in human erythrocytes. The Journal of biological chemistry 190 12584193
2010 Heat shock protein 90 as a drug target against protozoan infections: biochemical characterization of HSP90 from Plasmodium falciparum and Trypanosoma evansi and evaluation of its inhibitor as a candidate drug. The Journal of biological chemistry 139 20837488
2007 Chaperoning a cellular upheaval in malaria: heat shock proteins in Plasmodium falciparum. Molecular and biochemical parasitology 111 17307260
2012 Charged linker sequence modulates eukaryotic heat shock protein 90 (Hsp90) chaperone activity. Proceedings of the National Academy of Sciences of the United States of America 107 22315411
2016 A broad analysis of resistance development in the malaria parasite. Nature communications 102 27301419
2007 Systems analysis of chaperone networks in the malarial parasite Plasmodium falciparum. PLoS computational biology 94 17941702
2011 Intracellular protozoan parasites of humans: the role of molecular chaperones in development and pathogenesis. Protein and peptide letters 90 20955165
2009 Plasmodial heat shock proteins: targets for chemotherapy. FEMS immunology and medical microbiology 88 20041948
2003 The heat shock protein 90 of Plasmodium falciparum and antimalarial activity of its inhibitor, geldanamycin. Malaria journal 82 14514358
2001 Host chaperones are recruited in membrane-bound complexes by Plasmodium falciparum. The Journal of biological chemistry 80 11711553
2004 Recurrent fever promotes Plasmodium falciparum development in human erythrocytes. The Journal of biological chemistry 71 15339915
2010 A repurposing strategy identifies novel synergistic inhibitors of Plasmodium falciparum heat shock protein 90. Journal of medicinal chemistry 64 20349996
2011 Characterisation of the Plasmodium falciparum Hsp70-Hsp90 organising protein (PfHop). Cell stress & chaperones 59 22005844
2005 The FK506-binding protein of the malaria parasite, Plasmodium falciparum, is a FK506-sensitive chaperone with FK506-independent calcineurin-inhibitory activity. Molecular and biochemical parasitology 56 15850699
1994 Molecular characterization of the heat shock protein 90 gene of the human malaria parasite Plasmodium falciparum. Molecular and biochemical parasitology 56 7838176
2012 Harmine is a potent antimalarial targeting Hsp90 and synergizes with chloroquine and artemisinin. Antimicrobial agents and chemotherapy 52 22615284
2010 Structure of the ATP-binding domain of Plasmodium falciparum Hsp90. Proteins 52 20635416
2005 Plasmodium falciparum calcineurin and its association with heat shock protein 90: mechanisms for the antimalarial activity of cyclosporin A and synergism with geldanamycin. Molecular and biochemical parasitology 52 15811524
2021 A heat-shock response regulated by the PfAP2-HS transcription factor protects human malaria parasites from febrile temperatures. Nature microbiology 48 34400833
2015 Imidazopyridazine Inhibitors of Plasmodium falciparum Calcium-Dependent Protein Kinase 1 Also Target Cyclic GMP-Dependent Protein Kinase and Heat Shock Protein 90 To Kill the Parasite at Different Stages of Intracellular Development. Antimicrobial agents and chemotherapy 47 26711771
2010 Malaria heat shock proteins: drug targets that chaperone other drug targets. Infectious disorders drug targets 44 20334623
2014 Differences in conformational dynamics between Plasmodium falciparum and human Hsp90 orthologues enable the structure-based discovery of pathogen-selective inhibitors. Journal of medicinal chemistry 42 24580531
2015 Plasmodium falciparum Hop (PfHop) Interacts with the Hsp70 Chaperone in a Nucleotide-Dependent Fashion and Exhibits Ligand Selectivity. PloS one 40 26267894
2009 The complementation of yeast with human or Plasmodium falciparum Hsp90 confers differential inhibitor sensitivities. Molecular and biochemical parasitology 40 19320098
1994 Sequence, transcript characterization and polymorphisms of a Plasmodium falciparum gene belonging to the heat-shock protein (HSP) 90 family. Gene 38 7828879
2016 Inhibition of Plasmodium falciparum Hsp90 Contributes to the Antimalarial Activities of Aminoalcohol-carbazoles. Journal of medicinal chemistry 35 27312008
2010 Chaperone expression profiles correlate with distinct physiological states of Plasmodium falciparum in malaria patients. Malaria journal 35 20719001
2001 A novel tetratricopeptide repeat (TPR) containing PP5 serine/threonine protein phosphatase in the malaria parasite, Plasmodium falciparum. BMC microbiology 35 11737864
2018 Identification of Hsp90 Inhibitors with Anti-Plasmodium Activity. Antimicrobial agents and chemotherapy 34 29339390
2016 In vitro and in vivo anti-malarial activity of novel harmine-analog heat shock protein 90 inhibitors: a possible partner for artemisinin. Malaria journal 34 27903279
2013 A purine analog synergizes with chloroquine (CQ) by targeting Plasmodium falciparum Hsp90 (PfHsp90). PloS one 34 24098696
2007 Three-dimensional structure of heat shock protein 90 from Plasmodium falciparum: molecular modelling approach to rational drug design against malaria. Journal of biosciences 32 17536172
2013 Targeting Plasmodium falciparum Hsp90: Towards Reversing Antimalarial Resistance. Pathogens (Basel, Switzerland) 30 25436880
2019 Harmicines - harmine and cinnamic acid hybrids as novel antiplasmodial hits. European journal of medicinal chemistry 29 31812035
2022 Design and synthesis of harmiquins, harmine and chloroquine hybrids as potent antiplasmodial agents. European journal of medicinal chemistry 28 35551033
2021 General Structural and Functional Features of Molecular Chaperones. Advances in experimental medicine and biology 27 34569020
1988 Identification of a heat shock-like antigen in P. falciparum, related to the heat shock protein 90 family. Nucleic acids research 27 3060854
2017 Identification and characterization of the antiplasmodial activity of Hsp90 inhibitors. Malaria journal 26 28724415
1994 Immunogenicity and antigenicity of a Plasmodium falciparum protein fraction (90-110 kDa) able to protect squirrel monkeys against asexual blood stages. Vaccine 26 8303938
2012 Anti-malarial activity of geldanamycin derivatives in mice infected with Plasmodium yoelii. Malaria journal 24 22361388
2013 Heat shock protein 90 inhibitors as broad spectrum anti-infectives. Current pharmaceutical design 23 22920905
2009 Crystallographic structure of the tetratricopeptide repeat domain of Plasmodium falciparum FKBP35 and its molecular interaction with Hsp90 C-terminal pentapeptide. Protein science : a publication of the Protein Society 23 19691130
2013 A review of recent patents on the protozoan parasite HSP90 as a drug target. Recent patents on biotechnology 21 23002958
2001 Antibodies specific for heat shock proteins in human and murine malaria. Microbes and infection 21 11369272
2021 Inhibitors of the Plasmodium falciparum Hsp90 towards Selective Antimalarial Drug Design: The Past, Present and Future. Cells 20 34831072
2022 Hsp90 and Associated Co-Chaperones of the Malaria Parasite. Biomolecules 18 35892329
2021 Further investigation of harmicines as novel antiplasmodial agents: Synthesis, structure-activity relationship and insight into the mechanism of action. European journal of medicinal chemistry 17 34274829
2019 Structural studies of the Hsp70/Hsp90 organizing protein of Plasmodium falciparum and its modulation of Hsp70 and Hsp90 ATPase activities. Biochimica et biophysica acta. Proteins and proteomics 17 31525467
2014 Co-chaperones of Hsp90 in Plasmodium falciparum and their concerted roles in cellular regulation. Parasitology 17 24560171
2011 Target highlights in CASP9: Experimental target structures for the critical assessment of techniques for protein structure prediction. Proteins 17 22020785
2010 Characterization of Plasmodium falciparum co-chaperone p23: its intrinsic chaperone activity and interaction with Hsp90. Cellular and molecular life sciences : CMLS 17 20140477
2019 Plasmodium falciparum R2TP complex: driver of parasite Hsp90 function. Biophysical reviews 16 31734827
2024 Selective targeting of Plasmodium falciparum Hsp90 disrupts the 26S proteasome. Cell chemical biology 15 38492573
2023 Pharmacophore Model-Based Virtual Screening Workflow for Discovery of Inhibitors Targeting Hsp90. ACS omega 15 37867657
2021 Plasmodium berghei Hsp90 contains a natural immunogenic I-Ab-restricted antigen common to rodent and human Plasmodium species. Current research in immunology 15 35492393
2020 Biophysical analysis of Plasmodium falciparum Hsp70-Hsp90 organising protein (PfHop) reveals a monomer that is characterised by folded segments connected by flexible linkers. PloS one 15 32343703
2018 Novobiocin-ferrocene conjugates possessing anticancer and antiplasmodial activity independent of HSP90 inhibition. Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry 15 30542925
2018 In silico identification and evaluation of potential interaction of Azadirachta indica phytochemicals with Plasmodium falciparum heat shock protein 90. Journal of molecular graphics & modelling 15 30544005
2022 Inhibition of Plasmodium falciparum Hsp70-Hop partnership by 2-phenylthynesulfonamide. Frontiers in molecular biosciences 14 36177352
2020 Novel Harmicines with Improved Potency against Plasmodium. Molecules (Basel, Switzerland) 14 32977642
2019 Thermodynamic analysis of interactions of the Hsp90 with adenosine nucleotides: A comparative perspective. International journal of biological macromolecules 13 30797004
2020 Solution structure of Plasmodium falciparum Hsp90 indicates a high flexible dimer. Archives of biochemistry and biophysics 12 32679196
2014 Exploring in vitro and in vivo Hsp90 inhibitors activity against human protozoan parasites. Bioorganic & medicinal chemistry letters 12 25547934
2024 Discovery of harmiprims, harmine-primaquine hybrids, as potent and selective anticancer and antimalarial compounds. Bioorganic & medicinal chemistry 11 38677112
2023 The Plasmodium falciparum exported J domain proteins fine-tune human and malarial Hsp70s: pathological exploitation of proteostasis machinery. Frontiers in molecular biosciences 11 37457831
2021 Identification of Plasmodium falciparum heat shock 90 inhibitors via molecular docking. Bioorganic & medicinal chemistry letters 11 33513390
2017 Comparative studies of the low-resolution structure of two p23 co-chaperones for Hsp90 identified in Plasmodium falciparum genome. International journal of biological macromolecules 11 29191421
2014 Plasmodium falciparum Hop: detailed analysis on complex formation with Hsp70 and Hsp90. Biochemical and biophysical research communications 11 25482441
2013 Targeting heat shock protein 90 for malaria. Mini reviews in medicinal chemistry 11 24070209
2011 Molecular analysis of Plasmodium falciparum co-chaperone Aha1 supports its interaction with and regulation of Hsp90 in the malaria parasite. The international journal of biochemistry & cell biology 11 22100910
2025 Two sides of the same coin: heat shock proteins as biomarkers and therapeutic targets for some complex diseases. Frontiers in molecular biosciences 10 40051500
2023 Plasmodium-Resistant Indole Diterpenoid Biosynthesis Gene Cluster Derived from Aspergillus oryzae Was Activated by Exogenous P450 Gene Ast B. Journal of natural products 10 37257055
2021 Febrile temperature causes transcriptional downregulation of Plasmodium falciparum Sirtuins through Hsp90-dependent epigenetic modification. Molecular microbiology 10 33538363
2024 In silico screening of selective ATP mimicking inhibitors targeting the Plasmodium falciparum Grp94. Journal of biomolecular structure & dynamics 8 38498364
2024 Characterization and Inhibition of the Chaperone Function of Plasmodium falciparum Glucose-Regulated Protein 94 kDa (Pf Grp94). Proteins 8 39670568
2024 Plasmodium falciparum heat shock proteins as antimalarial drug targets: An update. Cell stress & chaperones 7 38518861
2023 Plasmodium female gamete surface HSP90 is a key determinant for fertilization. mBio 6 38131664
2024 Ursolic acid acetate and iso-mukaadial acetate bind to Plasmodium falciparum Hsp90, abrogating its chaperone function in vitro. Naunyn-Schmiedeberg's archives of pharmacology 5 38252299
2024 Auto QSAR-based active learning docking for hit identification of potential inhibitors of Plasmodium falciparum Hsp90 as antimalarial agents. PloS one 4 39585817
2025 Hsp90 and associates shaping parasite biology. mSphere 3 40990539
2025 Plasmodium knowlesi Heat Shock Protein 90s: In Silico Analysis Reveals Unique Druggable Structural Features. International journal of molecular sciences 1 41465491
2025 The possibilities and challenges associated with selective targeting Plasmodium falciparum Hsp90 for Malaria. Transactions of the Royal Society of South Africa. Royal Society of South Africa 1 41836916
2024 Study of the naturally occurring lignan brachangobinan A as antiplasmodial agent: Synthesis, biological evaluation, and in silico prediction. Chemico-biological interactions 1 39710055
2026 Synthetic quinolone-tethered aminoguanidine derivatives exhibit potent anti-plasmodial activity. International journal of antimicrobial agents 0 41921671
2026 Heat shock protein Gp96 (Grp94) in malaria: functional insights at the host-parasite interface and therapeutic perspectives. Frontiers in cell and developmental biology 0 41970953
2026 Data sets on the interaction of FKBP35 from Plasmodium knowlesi and Hsp90 C-terminal pentapeptide. Data in brief 0 42376286
2026 Plasmodium falciparum HSP90 inhibitors show divergent resistance despite a shared ATP-binding site. Cell reports 0 42406593
2026 In Silico Exploration of Antimalarial Potential of Ethanolic Leaf Extract of Heliotropium indicum. Nigerian journal of physiological sciences : official publication of the Physiological Society of Nigeria 0 42537022
2025 Investigation of a cryptic ligand binding site on Plasmodium falciparum Hsp90. Bioorganic & medicinal chemistry 0 40907219
2025 Shared Binding Site but Divergent Resistance Profiles Uncover Novel Resistance Mechanisms in Plasmodium HSP90 Inhibitors. bioRxiv : the preprint server for biology 0 41279590