|
Figure 4.
FIG. 4. Stereo view of the model of the inhibitor
34·human-uPA complex. The inhibitor is drawn as sticks
with atom dependent colors. For simplification, only the
hydrogens, which are attached to the terminal side chain
nitrogens of the P2 arginine, are shown. The protein is
visualized by a Connolly surface, blue and red surface areas
showing hydrogen acceptors and donators, respectively. Gray
areas have no hydrogen bonding properties. The guanidino group
of the Arg side chain in the P2 position of the inhibitor
probably forms a salt bridge (yellow lines with distances given
in Å) to the carboxyl group of Asp60A, found specifically
only in human uPA. This model was generated from the x-ray
structure of the inhibitor 27·  c-uPA complex (see Fig.
3) by replacement of the oxygen and phenyl ring in the Ser(Bzl)
side chain by a CH[2]- and guanidino group, respectively,
followed by energy minimization of the enzyme-inhibitor complex
using the software package Sybyl version 6.9.1. (Tripos).
|
