Figure 2.
(a) Surface topology of the CPD active site. Hydrophobic
residues in the substrate binding cleft are highlighted in
orange. The aza-peptide epoxide inhibitor (JCP598) is shown as a
stick model bound in the substrate binding pocket. The N
terminus is shown as a gray ribbon, terminating at Ile5 and
highlighting the threading of this region along the surface of
the core domain. (b) Close-up 'top' and 'bottom' views of the S1
pocket. Hydrophobic residues in the S1 pocket are shown as
orange sticks, and the side chain atoms of the P1 aza-leucine
residue are shown as transparent spheres. Hydrogen bonds between
the inhibitor backbone and the protein are shown as dashed
lines. (c) Superposition of the D and E -strands
of caspase-3–aza-Asp epoxide (PDB ID 2C1E) and
CPD–aza-leucine epoxide inhibitor structures shown as a
cut-away view of the thioether inhibitor adduct bound in the S1
pocket. Caspase-3 is colored purple, and the aza-Asp inhibitor
is colored pink. The MARTX[Vc] CPD is colored gray, and the
aza-leucine inhibitor is colored yellow.
The above figure is reprinted
from an Open Access publication published by Macmillan Publishers Ltd:
Nat Chem Biol
(2009,
5,
469-478)
copyright 2009.
-strands
of caspase-3–aza-Asp epoxide (PDB ID 2C1E) and
CPD–aza-leucine epoxide inhibitor structures shown as a
cut-away view of the thioether inhibitor adduct bound in the S1
pocket. Caspase-3 is colored purple, and the aza-Asp inhibitor
is colored pink. The MARTX[Vc] CPD is colored gray, and the
aza-leucine inhibitor is colored yellow.