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The structure of a Trypanosoma cruzi glucose‐6‐phosphate dehydrogenase reveals differences from the mammalian enzyme
Author(s) -
Mercaldi Gustavo F.,
Dawson Alice,
Hunter Willian N.,
Cordeiro Artur T.
Publication year - 2016
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12276
Subject(s) - pentose phosphate pathway , trypanosoma cruzi , cofactor , dehydrogenase , enzyme , biochemistry , glucose 6 phosphate dehydrogenase , trypanosoma , biology , substrate (aquarium) , chemistry , glycolysis , parasite hosting , virology , computer science , ecology , world wide web
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.