Figure 2.
FIGURE 2. Compound 9 bound in the COX active site of COX-1.
A, stereo view of 9 fitted into simulated annealing omit map
difference density (blue) contoured at 3 witha3Å boundary
around the ligand. Carbon atoms of 9 are colored green with
heteroatoms colored the same as in 1. B, chlorobenzoyl group of
9 is oriented toward the mouth of the active site; the methoxy
group of indole ring is oriented up into the top of the channel,
and the ethanolamide group with the (S)-ethyl substitution lies
within the side pocket region of the channel. Yellow dashed
lines represent various interactions (hydrophobic and
hydrophilic) between ligand and protein. The hydroxyl group of
the ethanolamide is oriented near the hydrophilic region (cyan)
of the side pocket making hydrogen bonds with residues Gln-192
and His-90 whereas the S-ethyl group is oriented into the more
hydrophobic region (pink) of the side pocket making van der
Waals interactions with Ile-523, Phe-518, and Ile-517. For
clarity, an additional polar interaction between Arg-120 and the
carbonyl of the chlorobenzoyl moiety is not shown.
witha3Å boundary
around the ligand. Carbon atoms of 9 are colored green with
heteroatoms colored the same as in 1. B, chlorobenzoyl group of
9 is oriented toward the mouth of the active site; the methoxy
group of indole ring is oriented up into the top of the channel,
and the ethanolamide group with the (S)-ethyl substitution lies
within the side pocket region of the channel. Yellow dashed
lines represent various interactions (hydrophobic and
hydrophilic) between ligand and protein. The hydroxyl group of
the ethanolamide is oriented near the hydrophilic region (cyan)
of the side pocket making hydrogen bonds with residues Gln-192
and His-90 whereas the S-ethyl group is oriented into the more
hydrophobic region (pink) of the side pocket making van der
Waals interactions with Ile-523, Phe-518, and Ile-517. For
clarity, an additional polar interaction between Arg-120 and the
carbonyl of the chlorobenzoyl moiety is not shown.