Figure 1.
Fig. 1. Structure of an allosteric inhibitor bound to
caspase-1. (a) 2F[o] - F[c] electron density for Compound 34
used for compound model building, contoured at 1 , is
shown as a blue mesh at the dimer interface (PDB ID code 2FQQ).
(b) Two molecules of Compound 34 are shown as spheres in the
central cavity at the dimer interface of caspase-1. (c) Residues
involved in forming the binding pocket for Compound 34 are shown
as spheres. Residues from the large subunit (Glu-241, Gln-257,
and Arg-286) are colored blue, and residues from the small
subunit (Thr-388, Glu-390, and Arg-391) are colored tan. (d)
Residues likely involved in the mechanism of inhibition of
caspase-1 by allosteric compounds are displayed. Arg-286
adjacent to the catalytic Cys-285 is located >12 Å from
Glu-390, to which it is salt-bridged in the active conformation.
The amide nitrogen of the linker group of Compound 34 is within
a hydrogen-bonding distance of the Glu-390 carboxylate. Arg-391
is shown to indicate the boundary of the binding pocket.
, is
shown as a blue mesh at the dimer interface (PDB ID code 2FQQ).
(b) Two molecules of Compound 34 are shown as spheres in the
central cavity at the dimer interface of caspase-1. (c) Residues
involved in forming the binding pocket for Compound 34 are shown
as spheres. Residues from the large subunit (Glu-241, Gln-257,
and Arg-286) are colored blue, and residues from the small
subunit (Thr-388, Glu-390, and Arg-391) are colored tan. (d)
Residues likely involved in the mechanism of inhibition of
caspase-1 by allosteric compounds are displayed. Arg-286
adjacent to the catalytic Cys-285 is located >12 Å from
Glu-390, to which it is salt-bridged in the active conformation.
The amide nitrogen of the linker group of Compound 34 is within
a hydrogen-bonding distance of the Glu-390 carboxylate. Arg-391
is shown to indicate the boundary of the binding pocket.