|
Figure 5.
FIGURE 5. Ligand-induced changes to Trp-741 and Met-895 in
stereo overlay and individually as space-fill representations.
a, comparison of the changes induced by DHT (slate) (Protein
Data Bank code 1I37 [PDB]
), R1881 (ruby) (Protein Data Bank code 1XQ2), R-3 (gold), and
S-1 (green) to the Trp-741, Met-745, Met-895 side chains. Notice
the different location of Met-745 in the DHT-bound structure
from displacement by the 19-methyl group, which causes the
Trp-741 side chain to also move relative to its position in
R1881. The Trp-741 indole ring is positioned similarly in R1881-
and R-3-complexed structures; however, the bromine atom on R-3
displaces the Met-895 side chain. Also notice the change in
position of the Trp-741 indole ring to allow accommodation of
the S-1 B-ring. b, changes in the position of Met-895 in the
W741L AR bound to S-1 (black) and R-bicalutamide (yellow).
Compared with the WT-S-1 complex, Met-895 moves toward the
Leu-741 side chain in the W741L-S-1 complex, compensating for
the loss of bulk in this mutant. In the W741L-R-bicalutamide
complex, the Met-895 side chain is wedged between the Leu-741
and the sulfonyl group of R-bicalutamide. Notice that the
position of the Met-895 side chain in the WT-S-1 complex would
be sterically precluded by the sulfonyl group of R-bicalutamide
in the presence of Trp-741.
|
