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Figure 2.
Figure 2. Effects of the 1X and 3X mutants on interactions
with TL-3. (a) Conformational changes observed at the P1/P1'
position of TL-3 in the 1X mutant protease. Comparisons of the
TL-3 complexes with wild-type protease (grey) and 1X protease
(yellow) reveals conformational changes at the P1/P1' position
of the inhibitor. The mutation of residue 82 from valine to
alanine in the 1X mutant protease weakens the packing contact
formed with the P1/P1' position of TL-3, allowing the P1/P1'
phenyl ring to shift away from the side-chain of Pro81 by 0.8
Å and rotate by 25° about the x1 torsion angle. (b)
Residues in the flap region of protease form stabilizing
contacts. The side-chain of Phe53 adopts two conformations in
wild-type and 1X proteases. In one conformation it forms a van
der Waals interaction with the side-chain of Met46. In the other
conformation it forms a hydrophobic contact with the P4 phenyl
ring of TL-3. The side-chain of Met46 is packed between the
side-chains of Phe53 and Lys55 in the wild-type and 1X
structures. In the 3X mutant protease residue 46 is mutated to
an Ile and residue 53 is mutated to a Leu (indicated in
parentheses). Loss of the stabilizing contacts due to these
mutations increases the overall mobility of the flaps (see
Figure 3(a)) and alters the water structure near the tips of the
flaps (see Table 2). The positions of Ile50, Gly51 and Gly52 are
indicated.
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