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

Autor(es)

Mercaldi, Gustavo F. ; Dawson, Alice ; Hunter, Willian N. ; Cordeiro, Artur T.

• Tipo de documento: Artigo Científico
• Fonte: FEBS Letters; v. 590, n. 16, p. 2776-2786, AUG 2016.
• Citações Web of Science: 5

Resumo

The enzyme glucose-6-phosphate dehydrogenase from Trypanosoma cruzi (TcG6PDH) 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 TcG6PDH obtained in a ternary complex with the substrate -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. (AU)

• Processo FAPESP: 13/03983-5 - Estudos funcionais e estruturais das enzimas relacionadas a produção de NADPH em trypanosomatídeos
• Beneficiário: Artur Torres Cordeiro
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/07533-7 - Estudos biofísicos de complexos da glicose 6-fosfato desidrogenase com inibidores
• Beneficiário: Gustavo Fernando Mercaldi
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado