Figure 6.

Structure based multiple surface sequence fragment alignment (sbMSFA) of a group of the MMP subfamilies. A) The topological tree of the subtree of the binding pockets for these MMP subgroups. The residue at corresponding positions from each member structure enters the alignment. For clarification we show only the sequence fragment for one representative structure for each subclass of MMPs. All residues in the alignment occur in the signature pocket, namely, their preservation ratio ρ > 50%. Residues that occur in the signature pocket with > 99% identical in residue type across all members are colored in blue, those between 75–99% identical are colored green, and those with < 75% identical residues are colored in gray. A special column colored in red represents a position that occurs in all subfamilies, but with a different residue type for each subfamily. This column corresponds to the X residue in the Pro221-X222-Tyr223 motif. For MMP-1 subfamily, there is in addition a signature residue (colored in red) that does not appear in other subfamilies. This corresponds to the key residue Arg198 that determines the depth of the S1’ pocket in MMP1 and hence is an important determinant of MMP1 specificity. B–D). Visualization of the underlying surfaces where the colored residues in A) are mapped onto the surface of the representative structure for each subfamily. B): a representatie structure of MMP-9, C) and D): a representative structure of MMP-1 with and without the key Arg residues for visualization of the effects of this Arg on the depth of the S1’ subsite.