5end

Crystal structure of beta-ketoacyl-acyl carrier protein reductase (FabG)(Q152A) from Vibrio cholerae

spinqualitylabelsall models 5end, resolution 2.55Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5end is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GOL Activity: [acyl-carrier-protein_reductase 3-oxoacyl-[acyl-carrier-protein] reductase], with EC number 1.1.1.100 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum Function [FABG_VIBCH] Catalyzes the NADPH-dependent reduction of beta-ketoacyl-ACP substrates to beta-hydroxyacyl-ACP products, the first reductive step in the elongation cycle of fatty acid biosynthesis. Publication Abstract from PubMed beta-ketoacyl-(acyl carrier protein) reductase (FabG) catalyzes the key reductive reaction in the elongation cycle of fatty acid synthesis (FAS), which is a vital metabolic pathway in bacteria and a promising target for new antibiotic development. The activation of the enzyme is usually linked to the formation of a catalytic triad and cofactor binding, and crystal structures of FabG from different organisms have been captured in either active or inactive conformations. However, the structural elements which enable activation of FabG require further exploration. Here we report structural, enzymatic, and binding studies of vcFabG, the FabG protein found in the causative agent of cholera, Vibrio cholerae. vcFabG exists predominantly as a dimer in solution and is able to self-associate to form tetramers, which is the state seen in the crystal structure. The formation of the tetramer may be promoted by the presence of the cofactor NADP(H). The transition between dimeric and tetrameric states of vcFabG is related to changes in the conformations of the alpha4/alpha5 helices on the dimer-dimer interface. Two glycine residues adjacent to the dimer interface (G92 and G141) are identified as the hinge for the conformational changes, while the catalytic tyrosine (Y155) and a glutamine residue that forms hydrogen bonds to both loops beta4-alpha4 and beta5-alpha5 (Q152) stabilize the active conformation. The functions of the aforementioned residues were confirmed by the binding and enzymatic assays for the corresponding mutants. IMPORTANCE: This paper describes structural, enzymatic, and binding studies of FabG from Vibrio cholera. In this work we dissect the structural elements responsible for the activation of vcFabG. The structural information provided here is essential for the development of antibiotics specifically targeting bacteria FabG, especially for the multi-drug resistant strains of V. cholerae. Dissecting the structural elements for the activation of beta-ketoacyl-(acyl carrier protein) reductase from Vibrio cholerae.,Hou J, Zheng H, Chruszcz M, Zimmerman MD, Shumilin IA, Osinski T, Demas M, Grimshaw S, Minor W J Bacteriol. 2015 Nov 9. pii: JB.00360-15. PMID:26553852 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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