Simulations of Shikimate Dehydrogenase from Mycobacterium tuberculosis in Complex with 3-Dehydroshikimate and NADPH Suggest Strategies for MtbSDH Inhibition

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Expression, purification and properties of shikimate dehydrogenase from Mycobacterium tuberculosis.

Tuberculosis, caused by Mycobacterium tuberculosis, continues to be one of the main diseases to mankind. It is urgent to discover novel drug targets for appropriate antimicrobial agents against this human pathogen. The shikimate pathway is considered as an attractive target for the discovery of novel antibiotics for its essentiality in bacteria and absence in mammalian cells. The Mycobacterium ...

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The crystal structure of shikimate dehydrogenase (AroE) reveals a unique NADPH binding mode.

Shikimate dehydrogenase catalyzes the NADPH-dependent reversible reduction of 3-dehydroshikimate to shikimate. We report the first X-ray structure of shikimate dehydrogenase from Haemophilus influenzae to 2.4-A resolution and its complex with NADPH to 1.95-A resolution. The molecule contains two domains, a catalytic domain with a novel open twisted alpha/beta motif and an NADPH binding domain w...

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ژورنال

عنوان ژورنال: Journal of Chemical Information and Modeling

سال: 2019

ISSN: 1549-9596,1549-960X

DOI: 10.1021/acs.jcim.8b00834