Figure 1.
Fig 1. Structural changes induced in Ras switch regions by
the glycine for alanine substitution at position 59. Close-up
view of Glu-37 (switch 1) and Arg-68 (switch 2) in the crystal
structures of wild-type Ras (A) (15) and RasA59G (B) in the
GppNp-bound forms. Switch 1 (SwI) and switch 2 (SwII) are in
magenta and yellow, respectively. Loop L4 and helix- 2 of
switch 2 are labeled. The GppNp and the Mg2+-ion are in light
blue, and water molecules (W) are represented by red spheres.
Tyr-32 is in pink, Glu-37 in red, and Arg-68 in blue. Hydrogen
bonds are represented by dashed lines and the van der Waals
interactions between Glu-37 and Tyr-71 (B) are indicated by a
dotted line. In wild-type Ras (A), Arg-68 stabilizes the N
terminus of the switch 2 region (60-62) through direct or
water-mediated hydrogen bonds. In RasA59G (B), Glu-37 makes
hydrogen bonds with Arg-68 and van der Waals interactions with
Tyr-71, which protects it partially from the solvent. Tyr-64,
which is essential for Sos-binding by Ras, adopts a position
that inhibits the docking of the two proteins. The catalytic
residue Gln-61 is positioned far from W175. Tyr-32 is making a
water-mediated hydrogen bond with the -phosphate, and its bulky
phenol group is protecting the phosphates from the surrounding
solvent. (C) Stereo representation of the superposition of the C
of
switch 1 and 2 regions between the structures of wild-type Ras
(green) and RasA59G (gold) in the GppNp-bound form. The residues
of L4 are shown, whereas only the side chains of Tyr-32, Glu-37,
Gln-61, Arg-68, and Tyr-71 are shown. The two water molecules
(W332 and W349) in wild-type Ras that coordinated Arg-68 and
that have been exchanged with the solvent on the reorientation
of the switch 2 region, are shown. Prepared with MOLSCRIPT (24)
and RASTER3D (25).
2 of
switch 2 are labeled. The GppNp and the Mg2+-ion are in light
blue, and water molecules (W) are represented by red spheres.
Tyr-32 is in pink, Glu-37 in red, and Arg-68 in blue. Hydrogen
bonds are represented by dashed lines and the van der Waals
interactions between Glu-37 and Tyr-71 (B) are indicated by a
dotted line. In wild-type Ras (A), Arg-68 stabilizes the N
terminus of the switch 2 region (60-62) through direct or
water-mediated hydrogen bonds. In RasA59G (B), Glu-37 makes
hydrogen bonds with Arg-68 and van der Waals interactions with
Tyr-71, which protects it partially from the solvent. Tyr-64,
which is essential for Sos-binding by Ras, adopts a position
that inhibits the docking of the two proteins. The catalytic
residue Gln-61 is positioned far from W175. Tyr-32 is making a
water-mediated hydrogen bond with the 
-phosphate, and its bulky
phenol group is protecting the phosphates from the surrounding
solvent. (C) Stereo representation of the superposition of the C