FIGURE 3.

Caspase-1 zymogen in comparison with other caspase-1 structures. A, surface representation of p35 C285A (PDB code 3E4C). The two monomers are colored wheat and slate, and the residues 286-298 are shown as spheres with their carbons colored green. Trp²⁹⁴ and Phe²⁹⁵ are located at the center of the dimeric protein. B, surface rendering of the ligand-free, active caspase-1 (PDB code 1SC1 (43)). The p20 and p10 are colored wheat and orange, respectively, in one subunit, and slate and dark blue in the other. The central cavity is left unoccupied in this protein because residues 286-298 (shown as spheres) are reoriented. A and B, Arg²⁴⁰ has been removed from the surface rendering for visualization of the central cavity. C, schematic representation of the subunit on the right shows the proximity of Asp²⁹⁷ to the adjacent catalytic site (Ala²⁸⁵ and His²³⁷) in the zymogen structure. D, B-factor putty (PyMol) indicates the thermal flexibility of the structure. One active-site loop has less flexibility then the other due to crystal packing. E, comparison of active-site loops with or without substrate mimetic. Residues 330-347 are shown as ribbons for the apo (ligand-free, purple, PDB code 1SC1 (43)), zymogen (blue, PDB code 3E4C), and active, inhibitor-bound structures (red, PDB code ICE1 (42)). The substrate mimetic in the inhibitor-bound structure, Ac-YVAD-CHO, is colored yellow. F, hydrophobic pocket binding allosteric inhibitors (gray sticks, PDB code 2FQQ (21)) and Trp²⁹⁴-Phe²⁹⁵ (green).