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Figure 3.
FIG. 3. Crystal structure of MR LBD bound to aldosterone
and progesterone. A, the overall fold of MR is very similar to
the other steroid receptors. B, helix 3 (magenta) residues
Asn770 and Ser767 form hydrogen bonds (yellow dashed lines) with
the loop (green) residue Glu955 preceding the AF-2 (red). Thr945
present on helix 10 (orange) plays a key role in receptor
activation by hydrogen bonding to the C-20 carbonyl and C-21
hydroxyl of aldosterone (yellow). C, close-up view of
MR-aldosterone hydrogen bond network. The 18-OH is positioned
for hydrogen bonding (yellow dashed lines) with the Asn770
carbonyl, whereas the Asn770 amide remains in position for
hydrogen bonding to the C-21 OH of aldosterone and Glu955, which
lies in the loop preceding the AF-2. Thr945, present on helix
10, forms a pair of hydrogen bonds with the C-20 and C-21
substituents of aldosterone. Cysteine 942 is in position to
interact with the 18-OH group to give aldosterone three
potential hydrogen bonds to helix 10. D, progesterone makes no
hydrogen bonds to Asn770. Multiple orientations of the Thr945
side chain hydroxyl were observed (A and B) in both
noncrystallographically related molecules. When the Thr945 side
chain hydroxyl is in the B position (green), the distance (black
dashed line) to the progesterone C-20 carbonyl makes hydrogen
bonding between the ligand and Thr945 unlikely.
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