The selectivity of galardin and an azasugar-based hydroxamate compound for human matrix metalloproteases and bacterial metalloproteases
Fig 6
Galardin and compound 1b docked into MMP-9 and galardin docked into pseudolysin.
Upper panel: The backbones of MMP-9 (5cuh) and pseudolysin (3dbk). The volume of the full binding pocket identified by the ICM Pocketfinder is displayed for both enzymes, with the S’1-subpocket indicated by an arrow. Middle panel: Galardin (red) and compound 1b (blue) docked into the binding pocket of MMP-9 and galardin (red) docked into pseudolysin. The panel shows that compounds may enter the S’1-subpocket of MMP-9 in a region between the side chains of Y423 and L188 on one side and the zinc. The corresponding entrance in pseudolysin is partly hindered by the side chain of R198. Lower panel: The complex from the middle section rotated 90 degrees and the ligands removed. The panel shows that the side chains of L188 and Y423 are located close to each other and hinder the entrance into the S’1-subpocket from the region above the zinc, while the corresponding region in pseudolysin is wider (side chains of N112 and L197).