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Figure 4.
Peptidomimetic inhibitors bound to the proteases. A, the
active site of CVB3 3C^pro with the bound TG-0204998. Protein is
rendered as a semitransparent solvent-accessible surface with
associated protein backbone and side chain atoms. The oxygen
atoms are shown in red, nitrogen in blue, sulfur in yellow, and
protein carbon atoms in magenta. The inhibitor atoms are shown
as ball-and-stick form and colored in orange for carbon. The
sulfur atom of Cys^147 is covalently attached to the inhibitor
carbon. The substrate binding subsites are designated as S1′,
S1, S2, S3, and S4. B, conserved water molecules, identified by
superimposing the two molecules of CVB3 3C^pro C147A mutant on
the TG-0204998 complex of CVB3 3C^pro. The water molecules are
shown here as spheres colored green/orange (C147A) and magenta
(complex). The protein model of the TG-0204998 complex structure
is shown as an electrostatic surface and TG-0204998 as sticks.
The conserved water molecules of the C147A mutant structure in
the active site are marked. The black star indicates the Michael
addition site. C and D, the active site of SARS 3CL^pro with
bound TG-0204998 (C) and TG-0205486 (D), colored as in A. The
substrate-binding subsites are also indicated.
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