Previously determined crystal structures show that compounds 1b and 1c share a substratelike pterin orientation in the complex with LmPTR1. In the same crystal structure, compound 1b also adopts a second, so-called inhibitor-like (or MTX-like) orientation, with the bicyclic ring system flipped by 180° and rotated by 30° (Figures and). Dual binding modes have also been observed in crystallographic complexes of TbPTR1 with small pteridine-based inhibitors. We here determined the crystal structure of the ternary complex of TbPTR1 with NADPH/NADP + and the reference compound 1b (PDB-ID 6rx5, resolution 1.42 Å, experimental details: Tables ). It shows that the diaminopteridinyl moiety of 1b adopts only the MTX-like orientation (Figure ), resembling its MTX-like binding mode in LmPTR1