FIGURE 3.

Superposition of the structure of M. tuberculosis VapBC-5 with its structural homologues. In all figures, M. tuberculosis VapB-5 is shown in green, M. tuberculosis VapC-5 is in magenta, Ngo FitA (34) is in orange, Ngo FitB (34) is in red, and Pae VapC (14) is in blue. A, ribbon diagram of the superimposed M. tuberculosis VapBC-5 and Pae VapC, which shows that the structure between these two homologues is conserved except for helix α-2 in VapBC-5 that is shifted. B, top view of the zoomed region showing the large displacement of M. tuberculosis VapC-5 helix α-2 compared with the corresponding helix in Pae VapC-5. The disorganized loop linkingα-1 toα-2 is represented as red broken lines. C, ribbon diagram of the superimposed structures. The structure of the toxins in these different structural homologues is conserved whereas their respective cognates differ. D, zoom of the acidic cavity of the superimposed structures. It shows that Arg-112 from M. tuberculosis VapC-5 and Arg-68 from Ngo FitA both form hydrogen bonds with a residue that belongs to the active site and thus Arg-112 could play an indirect role in the mechanism of inhibition of the toxin. Residues from M. tuberculosis VapB-5 are shown as green sticks, those from M. tuberculosis VapC-5 are shown in yellow, Arg-68 from Ngo FitA is in orange, and active site residues from Ngo FitB are shown as red sticks. E, stereoview of the superposition of the putative active site residues of M. tuberculosis VapC-5 with the active site residues and magnesium ions of endo and exonuclease FEN-1 (31). Residues from M. tuberculosis VapC-5 are shown as yellow sticks, and active site residues and magnesium ions from endo and exonuclease FEN-1 are shown as gray sticks and green spheres, respectively. The conservation of most of the residues that bind the magnesium ions suggests that M. tuberculosis VapC-5 catalytic mechanism could involve the two metal ions as suggested by the mechanism of FEN-1 nuclease.