Fig. 3: Concealed redox cycle catalysed by BurG. | Nature Chemistry

Fig. 3: Concealed redox cycle catalysed by BurG.

From: Pathogenic bacteria remodel central metabolic enzyme to build a cyclopropanol warhead

Fig. 3

a, Gonydiol 5 transformation assay with NAD+-free BurG with addition of NAD+, NADH or in the absence of cofactor; top: 6 as reference. b, Full view of the 3D structure of BurG co-crystallized with the KARI inhibitor 7 (left). A and B, subunits; N and C, termini. The black rectangle displays the area for the zoom in the substrate binding channel (middle) and active site zoom (right) (PDB 7PCG). GOL, glycerol. c, Steady-state kinetics of NADH-mediated reduction of hydroxypyruvate 8 to glyceric acid 9 through BurG; mean and standard deviation as obtained from two independent protein preparations (n = 2). d, Scheme of the transformation of hydroxamate 10 to hemiaminal 11. e, 3D structure of BurG co-crystallized with 11 after incubation with 10 and NADH (PDB 7PCL). Two magnesium atoms (A and B) are shown as green spheres. f, BurG-mediated oxidation of carba-gonydiol 12 to the enolate 13. g, 3D structure of BurG with 13 obtained after co-crystallization with 12 and NAD+ (PDB 7PCM). h, Single amino acid substitution (E232Q) renders BurG inactive. i, 3D structure of BurG E232Q co-crystallized with 12 (PDB 7PCO).

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