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Figure 5.
FIG. 5. Close-up views of the MR C808S/S810L mutant bound
to progesterone, cortisone, and spironolactone. A, an overlay of
progesterone (yellow) in MR C808S (cyan) and progesterone (pink)
in MR C808S/S810L (pink) binding pockets indicates that the
S810L mutation has no measurable effect on ligand position or
orientation. Hydrogen bonding networks (yellow dashed lines) are
indicated. Van der Waals interactions are indicated by black
dashed lines. Multiple orientations of the Thr945 side chain
hydroxyl were observed (A and B) in both noncrystallographically
related molecules. B, the C-11 carbonyl of cortisone (blue) does
not interact with MR C808S/S810L (orange) residue Asn770 and is
 2.9
Å away from the backbone carbonyl of Leu769. C, the
lactone keto group of spironolactone (white) is 3.7
Å away from Asn770 in MR C808S/S810L (magenta), suggesting
a weakened potential for hydrogen bonding to Asn770. Again,
multiple orientations of the Thr945 side chain hydroxyl were
observed (A and B) in both noncrystallographically related
molecules. Similar to that observed with progesterone, the
distance from the hydroxyl of Thr945 to the lactone keto moiety
of spironolactone differs depending upon the orientation of this
residue. The weak interaction of spironolactone with both Asn770
and Thr945 is probably the basis for the antagonism observed
with this steroid.
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