KEY RESOURCES TABLE.

REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
GFP Antibody (B-2) Alexa Fluor® 488	Santa Cruz Biotechnology	Cat# sc-9996 AF488
HisProbe™-HRP Conjugate	ThermoFisher Scientific	Cat# 15165
Bacterial and virus strains
BL21 (DE3)	New England Biolabs	Cat# C2527
NEB5α	New England Biolabs	Cat# C2987
Biological samples
Human Blood	Gulf Coast Regional Blood Center	N/A
P. berghei ANKA infected Anopheles stephensi mosquitoes	University of Georgia SporoCore	N/A
Chemicals, peptides, and recombinant proteins
Ni-NTA agarose	Qiagen	Cat# 30210
cOmplete Ultra EDTA-free	Sigma-Aldrich	Cat# 5892953001
CNBR-Activated Sepharose 4B	Cytiva Life Sciences	Cat# 17043001
ATP-Sepharose	This paper	N/A
Q5® High-Fidelity DNA Polymerase	New England Biolabs	Cat# M0491
Geldanamycin-FITC	Sigma-Aldrich	Cat# SML1277
XL888	BPS Bioscience	Cat# 27781-1
BX-2819	This paper	N/A
Tropane 1	This paper	N/A
HS292	This paper	N/A
SYBR™ Green I	Invitrogen	Cat# S7563
Geldanamycin	TCI Chemicals	Cat# G0334
Bortezomib	Selleck Chemical	Cat# S1013
Suc-Leu-Leu-Val-Tyr-AMC	Cayman Chemical	Cat# 10008119
Cycloheximide	Cayman Chemical	Cat# 14126
Epoxomicin	Cayman Chemical	Cat# 10007806
His6-PfHsp90-GFP	This paper	N/A
PfHsp90-His6	This paper	N/A
HsHsp90-His6	This paper	N/A
T7-HsHsp90-NBD-His6	This paper	N/A
T7-HsHsp90-NBD(E25D/K112R)-His6	This paper	N/A
T7-HsHsp90-NBD(Q23N)-His6	This paper	N/A
T7-HsHsp90-NBD(L122I/G125S/A126G)-His6	This paper	N/A
T7-PfHsp90-NBD-His6	This paper	N/A
Critical commercial assays
Pierce™ Coomassie Plus Bradford Assay	Thermo Fisher Scientific	Cat# 23236
Bright-Glo™ Luciferase Assay System	Promega	Cat# G6081
CellTiter-Fluor™ Cell Viability Assay	Promega	Cat# E2620
Hemacolor® Stain Set	Sigma-Aldrich	Cat# 65044-93
TMT10plex Isobaric Label Reagent Set	Thermo Fisher Scientific	Cat# 90406
Pierce High pH Reversed-Phase Peptide Fractionation Kit	Thermo Fisher Scientific	Cat# 84868
Q5® Site-Directed Mutagenesis Kit	New England Biolabs	Cat# E0554S
Deposited data
Thermal proteome profiling raw data	This paper	PXD040417
Small molecule screen results	This paper	20240206085657
Experimental models: Cell lines
Human: Huh7 cells	Sigma-Aldrich	Cat# 01042712-1VL
Experimental models: Organisms/strains
P. falciparum 3D7	BEI Resources Repository	NIAID, NIH, MRA-102
P. falciparum NF54 peg4-tdTomato	Laboratory of Photini Sinnis	N/A
P. berghei-Luc ANKA	University of Georgia SporoCore	N/A
Oligonucleotides
Primers for cloning and mutagenesis, see Table S3	This paper	N/A
Recombinant DNA
His6-PfHsp90-GFP (pET-45b)	This paper	N/A
PfHsp90-His6 (pET-21b)	Posfai et al.26	N/A
HsHsp90-His6 (pET-21b)	Posfai et al.26	N/A
T7-HsHsp90-NBD-His6 (pET-21a)	This paper	N/A
T7-HsHsp90-NBD(E25D/K112R)-His6 (pET-21a)	This paper	N/A
T7-HsHsp90-NBD(Q23N)-His6 (pET-21a)	This paper	N/A
T7-HsHsp90-NBD(L122I/G125S/A126G)-His6 (pET-21a)	This paper	N/A
T7-PfHsp90-NBD-His6 (pET-21a)	This paper	N/A
Software and algorithms
ChemDraw Professional 18.0	PerkinElmer	https://www.perkinelmer.com/category/chemdraw
GraphPad Prism 9	GraphPad software	graphpad.com
Schrödinger Release 2023-1: Maestro	Schrödinger, LLC	https://www.schrodinger.com/products/maestro
Clustal Omega	Madeira et al.94	https://www.ebi.ac.uk/Tools/msa/clustalo/
STRING database	Szklarczyk et al.49	https://string-db.org/
Cytoscape 3.10.1	Shannon et al.103	https://cytoscape.org/
PlasmoDB	The Plasmodium Genome Database Collaborative104	https://plasmodb.org/plasmo/app/
REVIGO	Supek at al.105	http://revigo.irb.hr/
Image Lab 6.1	Bio-Rad	https://www.bio-rad.com/en-us/product/image-lab-software?ID=KRE6P5E8Z
Other
0.2 μm PVDF membrane filter plate	Corning	Cat# 3505
Non-treated black 96 well plates	Corning	Cat# 3915
Non-binding black 384 well plates	Corning	Cat# 3575
Tissue culture treated white 384 well plates	Corning	Cat# 3570
NuPAGE 3–8% tris-acetate polyacrylamide gel	Thermo Fisher Scientific	Cat# EA0375BOX