, All chemicals were purchased from Sigma Aldrich (St. Quentin Fallavier, France), unless otherwise stated and the protease inhibitor cocktail was from Roche

G. Healthcare, . Sigma-aldrich, and . St, Quentin Fallavier, France) with the type II restriction enzymes BamHI and XhoI for glutathione S-transferase (GST) fusion at the N-terminus (GenScript) Plasmids were transformed into chemically competent E. coli BL21(DE3), which were grown overnight at 37 ? C in 2 × YT medium containing 100 µg/mL ampicillin. These cultures were used to inoculate 1 L volumes of 2 × YT medium (containing 100 µg/mL ampicillin) in 5 L flasks. The cultures were allowed to grow at 37 ? C before the temperature was decreased to 18 ? C. At an optical density at 600 nm (OD600) of about 1.0, protein expression was induced overnight at 18 ? C with 0.1 mM isopropyl ?-D-1-thiogalactopyranoside (IPTG) The bacteria were harvested by centrifugation and were frozen at ?20 ? C. Cells were resuspended in a lysis buffer mM PMSF) in the presence of protease inhibitor cocktail (Roche), and lysozyme was added to 1 mg/mL and incubated 1 h at 4 ? C with gentle agitation) were added to degrade nucleic acids and decrease sample viscosity. After centrifugation at 4 ? C, the soluble fraction was collected and proteins were bound to Glutathione sepharose 4B beads (GE Healthcare) Beads were washed three times with lysis buffer and once, Production and Purification of the Parasitic Kinases The parasitic kinase genes (Supplementary Data, Table S3) were optimized for expression in E. coli Cells were then sonicated on ice before 6 mM MgCl 2 and 25 U/mL benzonase mM MgCl 2 , 2 mM DTT, 1 mM sodium vanadate). Proteins were eluted with elution buffer (buffer C containing 30 mM reduced glutathione, 15% glycerol, p.15

, Protein Kinase Assays Kinase activities were assayed in buffer A or C at 30 ? C at a final ATP concentration of 15 µmol/L. Blank values were subtracted and activities were expressed in percent of the maximal activity, i.e., in the absence of inhibitors. Controls were performed with appropriate dilutions of DMSO. The GS-1, CKS, CDK7/9 tide and RS peptide substrates were obtained from Proteogenix

, (human, recombinant) were prepared as previously described [6,7] Their kinase activity was assayed in buffer A, with 1 mg histone H1/mL, in the presence of 15 µmol/L [?-33 P] ATP (3000 Ci/mmol; 10 mCi/mL) in a final volume of 30 µL After 30 min incubation at 30 ? C, the reaction was stopped by harvesting onto P81 phosphocellulose supernatant (Whatman, Dutscher SAS, Brumath, France) using a FilterMate harvester (PerkinElmer, Courtaboeuf, France) and were washed in 1% phosphoric acid. Scintillation fluid was added and the radioactivity measured in a Packard counter. CDK9/cyclin T (human, recombinant, expressed in insect cells) was assayed as described for CDK1/cyclin B, but using CDK7/9 tide (YSPTSPSYSPTSPSYSPTSPSKKKK) (8.1 µg/assay) as a substrate. GSK-3?/? (porcine brain, native) and PfGSK3 (plasmodium falciparum, recombinant, expressed in E. coli as GST fusion proteins) was assayed, CDK1/cyclin B (M phase starfish oocytesYRRAAVPPSPSLSRHSSPHQSpEDEEE) (pS stands for phosphorylated serine), a GSK-3 specific substrate, p.1

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