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Figure 3.
Fig. 3. Structural analysis of mutations in the allosteric
circuit of caspase-1. (a) A network of interactions across the
dimer interface of caspase-1 in the z-VAD-FMK-inhibited protein.
The inhibitor is shown as yellow sticks in the upper left and
lower right. The active-site Cys-285 and Arg-286 are displayed
as blue sticks, Glu-390 at the dimer interface as tan sticks,
and a water molecule mediating the interaction between the two
Glu residues is shown as a red sphere. (b) The x-ray crystal
structure of each allosteric-circuit mutant was determined in
the presence of the active-site inhibitor z-VAD-FMK. All
structures (PDB ID codes 2FQS, R286A; 2FQU, E390A; and 2FQV,
R286A/E390A) adopted a dimeric structure very similar to that of
the wild-type enzyme in complex with an active-site inhibitor
(PDB ID code 2FQR). No significant conformational changes were
observed in the enzymes except for those involving residues in
the allosteric circuit. The 2F[o] - F[c] electron density for
residues Arg-286, Glu-390, and Thr-388 is displayed. (Bottom
Left) The position of Compound 34 displayed as spheres. (Bottom
Right) The ligand-free (apo) conformation of caspase-1.
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