To establish the binding mode of the tool PfCLK3 inhibitor TCMDC-135051 (1) we report here a co-crystal structure of PfCLK3 kinase domain in complex with TCMDC-135051 (1) to 2.1 Å resolution (Fig. , PDB: 8RPC). The structure resembles our previously published molecular modelling of TCMDC-135051 (1) in a homology model (generated using SWISS-MODEL and the kinase domain structure of the closest mammalian orthologue PRPF4B as a template) with an RMSD of 1.08 Å, yet with several important differences (Fig. ). The azaindole scaffold of TCMDC-135051 (1) binds as predicted to the ATP-binding site, in the flipped orientation, forming hydrogen bonds with the amide backbone of Met447 (Fig. ). However, the core sits closer to the hinge loop and further out of the binding site than predicted, which allows the diethylamine to form a charge-dipole interaction in the crystal structure with the backbone carbonyl of Trp448 (Fig. ). The carboxylic acid-Lys394 interaction predicted in the docking studies is mediated by three water molecules as seen in the crystal structure (Fig. ), which sit in the pocket forming a network of interactions with three other residues Cys510, Asp511 and Ser377 (Fig. ). Interestingly, the isopropyl group does not displace these waters to sit in the hydrophobic pocket next to the Phe444 gatekeeper as predicted (Fig. ). Surprisingly, this lipophilic functionality appears to protrude out of the pocket towards the solvent exposed space (Fig. ).