Titre :

Binding of NADP+ triggers an open-to-closed transition in a mycobacterial FabG β-ketoacyl-ACP reductase

Auteur(s) :

Blaise, Mickaël [Auteur]
Centre d’études d’Agents Pathogènes et Biotechologies pour la Santé [CPBS]
Van Wyk, Niël [Auteur]
Centre d’études d’Agents Pathogènes et Biotechologies pour la Santé [CPBS]
Banères-Roquet, Françoise [Auteur]
Centre d’études d’Agents Pathogènes et Biotechologies pour la Santé [CPBS]
Guerardel, Yann [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Kremer, Laurent [Auteur]
Centre d’études d’Agents Pathogènes et Biotechologies pour la Santé [CPBS]

Titre de la revue :

The Biochemical Journal

Nom court de la revue :

Biochem. J.

Numéro :

474

Pagination :

907-921

Date de publication :

2017-03-07

ISSN :

1470-8728

Mot(s)-clé(s) en anglais :

Mycobacterium
FabG
crystallography
short-chain dehydrogenase/reductase
β-ketoacyl reductase

Discipline(s) HAL :

Chimie/Chimie théorique et/ou physique

Résumé en anglais : [en]

The ketoacyl-acyl carrier protein (ACP) reductase FabG catalyzes the NADPH/NADH dependent reduction of β-ketoacyl-ACP substrates to β-hydroxyacyl-ACP products, the first reductive step in the fatty acid biosynthesis ...
Lire la suite >The ketoacyl-acyl carrier protein (ACP) reductase FabG catalyzes the NADPH/NADH dependent reduction of β-ketoacyl-ACP substrates to β-hydroxyacyl-ACP products, the first reductive step in the fatty acid biosynthesis elongation cycle. FabG proteins are ubiquitous in bacteria and are part of the type II fatty acid synthase system. Mining the Mycobacterium smegmatis genome uncovered several putative FabG-like proteins. Among them, we identified M. smegmatis MSMEG_6753 whose gene was found adjacent to MSMEG_6754, encoding a recently characterized enoyl-CoA dehydratase, and to MSMEG_6755, encoding another potential reductase. Recombinantly expressed and purified MSMEG_6753 exhibits ketoacyl reductase activity in the presence of acetoacetyl-CoA and NADPH. This activity was subsequently confirmed by functional complementation studies in a fabG thermosensitive Escherichia coli mutant. Furthermore, comparison of the apo and the NADP(+)-bound MSMEG_6753 crystal structures showed that cofactor binding induces a closed conformation of the protein. A ΔMSMEG_6753 deletion mutant could be generated in M. smegmatis, indicating that this gene is dispensable for mycobacterial growth. Overall, these results showcase the diversity of FabG-like proteins in mycobacteria and new structural features regarding the catalytic mechanism of this important family of enzymes that may be of importance for the rational design of specific FabG inhibitors.Lire moins >

Langue :

Anglais

Audience :

Non spécifiée

Établissement(s) :

CNRS
Université de Lille

Collections :

• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Équipe(s) de recherche :

Chemical Glycobiology

Date de dépôt :

2020-02-12T15:11:13Z
2021-03-11T12:52:46Z