Figure 1.
FIGURE 1. Compound 8 bound in the COX active site of COX-1.
A, stereo view of 8 bound in COX active site with simulated
annealing omit map difference density (blue) contoured at 3 witha3Å boundary
around the ligand. Various residues within the active site are
shown with carbons for 8 shown in orange, oxygen red, nitrogen
blue, and chlorine purple. B, stereo representation of 8 bound
in the COX site in the same manner as the parent compound
indomethacin; the chlorobenzoyl group is oriented up toward the
top of the channel, the methoxy group on indole ring points
toward the side pocket (Leu-517, Phe-518, Ile-523, Gln-192, and
Ser-516), and the ethanolamide group with the R-ethyl
substitution sits next to Arg-120 and Tyr-355 at the mouth of
the active site. Carbon atoms of 8 are shown with same color
scheme as in A with the yellow dashed lines representing various
interactions (hydrophilic) between ligand and protein residues.
The hydroxyl group of the ethanolamide group makes a hydrogen
bond with Arg-120 and Glu-524, whereas the (R)-ethyl group is
positioned just outside the mouth of the active site. Refinement
statistics for both structures are shown in Table 2. All figures
presented here were created using the program PyMOL.
witha3Å boundary
around the ligand. Various residues within the active site are
shown with carbons for 8 shown in orange, oxygen red, nitrogen
blue, and chlorine purple. B, stereo representation of 8 bound
in the COX site in the same manner as the parent compound
indomethacin; the chlorobenzoyl group is oriented up toward the
top of the channel, the methoxy group on indole ring points
toward the side pocket (Leu-517, Phe-518, Ile-523, Gln-192, and
Ser-516), and the ethanolamide group with the R-ethyl
substitution sits next to Arg-120 and Tyr-355 at the mouth of
the active site. Carbon atoms of 8 are shown with same color
scheme as in A with the yellow dashed lines representing various
interactions (hydrophilic) between ligand and protein residues.
The hydroxyl group of the ethanolamide group makes a hydrogen
bond with Arg-120 and Glu-524, whereas the (R)-ethyl group is
positioned just outside the mouth of the active site. Refinement
statistics for both structures are shown in Table 2. All figures
presented here were created using the program PyMOL.