Figure 3

Ligation-state conformational changes in thermolysin. (a) Backbone of thermolysin structure [PDB:1FJT] with coordinated valine-lysine dipeptide in red and motif residues shown in blue. Side-chains of the motif residues are shown for reference, but only C _α coordinates are used by LabelHash in this paper. The yellow, semi-transparent volume corresponds to the superimposed benzylsuccinic acid ligand of [PDB:1HYT]. The coordinated Zn²⁺ ion is depicted as a small green sphere in the center of the motif residues. The binding positions of the two ligands are superimposed to illustrate where the occupied regions of the thermolysin binding site differ between the two ligands. (b) Applying FASST to the family of thermolysin structures reveals that apo and holo structures segregate into different regions of the SCs. The segregation of structures seen indicates that the motif residues undergo conformational change upon binding a ligand. The location of particular structures in the SCs are labeled for reference. Light gray ellipses denote automatically identified clusters. The open/closed plot characters correspond to apo/holo structures, respectively. (c), (d) Holo outlier structures [PDB:1FJT] and [PDB:1FJW] with bound valine-lysine dipeptide and phenol ligands, respectively; the ligand of both structures sits in the side-chain recognition pocket but does not induce conformation change of the motif residues. (e), (f), (g) Ligated inhibitors from [PDB:5TLN], [PDB:1PE5], and [PDB:1HYT], respectively, in semi-transparent yellow superimposed with the [PDB:1FJT] binding site. These 3 inhibitors interact directly with the coordinated Zn²⁺ ion and induce conformational change in the binding site.