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Figure 3.
Figure 3. Crystal structures of PR mutants in complex with
NFV. (a) Two orientations of NFV in the mutant PR active site.
The 2F[o]–F[c] electron density map is contoured at the 1.0σ
level. The carbon atoms for the two NFV conformations are
colored yellow and light red, respectively. Oxygen, nitrogen and
sulfur atoms are colored red, blue and gold, respectively.
Catalytic aspartate residues are shown with carbon atoms colored
gray. (b) Superposition of D30N mutant with wild-type complex
structure. Top view of the PR active site. Nelfinavir with
residues 30 are shown in stick representation with the carbon
atoms are colored gray and light red for the wild-type and D30N
mutant, respectively. Oxygen, nitrogen and sulfur atoms are
colored red, blue and gold, respectively. (c) Close van der
Waals contact of the M90 side-chain with the main-chain of the
catalytic residue. Van der Waals surfaces are shown as meshes
for catalytic aspartate and residue 90 in the D30N mutant and
the D30N/L90M mutant. (d) Hydrogen bond network formed by
residue 88 in wild-type and D30/N88D PR. The wild-type structure
is represented by gray carbon atoms, while the mutant structure
is represented by green carbon atoms. Water molecules (shown as
spheres) are colored correspondingly. Hydrogen bonds are
represented by dotted lines. The water mediated contact between
D88 and N30 in the mutant structure is represented by red lines.
(e) Plot showing the RMSDs for the positions of main-chain and
side-chain atoms of individual residues after superimposition of
the D30N PR and D30N/A71V PR structures.
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