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

Gustavo F. Mercaldi, Alice Dawson, William N. Hunter, Artur T. Cordeiro (Lead / Corresponding author)

Research output: Contribution to journalLetter

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Abstract

The enzyme glucose-6-phosphate dehydrogenase from Trypanosoma cruzi (TcG6PDH) catalyses the first step of the pentose phosphate pathway 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 glucose-6-phosphate 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. This article is protected by copyright. All rights reserved.

Original languageEnglish
Pages (from-to)2776-2786
Number of pages11
JournalFEBS Letters
Volume590
Issue number16
Early online date19 Jul 2016
DOIs
Publication statusPublished - 19 Aug 2016

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