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

Abstract:

: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 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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Mercaldi GF,Dawson A,Hunter WN,Cordeiro AT

doi

10.1002/1873-3468.12276

subject

Has Abstract

pub_date

2016-08-01 00:00:00

pages

2776-86

issue

16

eissn

0014-5793

issn

1873-3468

journal_volume

590

pub_type

信件
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    authors: Cross RA

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    authors: Iswari S,Krishnamurthy DS,Jacob TM

    更新日期:1985-09-23 00:00:00

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    更新日期:2009-07-21 00:00:00

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    authors: Kirk K,Kirk J

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    更新日期:2001-11-30 00:00:00

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    authors: Fischer HG,Eder C

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    authors: Nojima H

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    更新日期:2004-06-18 00:00:00

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    更新日期:1994-03-07 00:00:00