|
Figure 4.
Fig 4. Nucleophilic attack trajectories for
protease/inhibitor complexes. (A) The geometric parameters
describing the nucleophilic attack trajectory are
diagrammatically defined.  [y] is the angle defined
by the enzyme serine  -oxygen, the inhibitor
carbonyl carbon, and the inhibitor carbonyl oxygen. [x] is
the angle between (i) the plane defined by the enzyme serine
-oxygen, the inhibitor
carbonyl carbon, and the inhibitor carbonyl oxygen, and (ii) the
plane defined by the peptide bond. O--C represents the
distance between the enzyme serine -oxygen and the inhibitor
carbonyl carbon. (B) Plot of [y] vs. [x]. Blue
triangles represent the structures of 78 protease/inhibitor
complexes, the orange circle represents the subtilisin/CI2
complex, and the red square represents the thrombin/fibrinogen
analog structure (16). The peptide bond diagrammed in the
background is for illustrative purposes. (C and D) Two views of
the superposition of 79 protease/inhibitor complexes, including
subtilisin/CI2. Superpositioning was based on the  -carbon
and carbonyl oxygen of the P[1] residue, and the amide nitrogen
of the P  residue,
which overlay closely for all structures. The red spheres
represent the relative positions of the enzyme serine -oxygen
for each structure. The outlying structure apparent in B, C, and
D is that of an ecotin mutant complexed with trypsin.
|
