The structure of a Trypanosoma cruzi glucose‐6‐phosphate dehydrogenase reveals differences from the mammalian enzyme

The enzyme glucose‐6‐phosphate dehydrogenase from Trypanosoma cruzi ( Tc G6PDH) catalyses the first step of the pentose phosphate pathway (PPP) and is considered a promising target for the discovery of a new drug against Chagas diseases. In the present work, we describe the crystal structure of Tc G6PDH obtained in a ternary complex with the substrate β‐ d‐ glucose‐6‐phosphate (G6P) and the reduced ‘catalytic’ cofactor NADPH, which reveals the molecular basis of substrate and cofactor recognition. A comparison with the homologous human protein sheds light on differences in the cofactor‐binding site that might be explored towards the design of new NADP + competitive inhibitors targeting the parasite enzyme.