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Figure 3.
Figure 3. Stereo views of selected receptor-hGH
interactions. In these panels, the receptor is colored green and
hGH in red, water molecules are shown as red spheres, and broken
lines represent hydrogen bonds. Alanine mutagenesis studies
reveal that the pockets shown in (a) and (b) contain side-chains
that are critical for high-affinity binding, whereas side-chain
interactions shown in (c) and (d) have little effect on binding.
(a) The binding pocket for Trp104. Loop EF[N] (residues 101 to
106) of the receptor interacts with residues on helix 4 (168 to
176) and 60 to 63 of hGH. A well-ordered water molecule (B=24
Å^2) bridges between the carbonyl atoms of residues Ser102
and Pro106 and the amide of Ile105. (b) The binding pocket for
Trp169. Trp169 of loop BC[C] and Arg43 of loop AB[N] interact
with residues 171 to 179 of helix 4 of hGH, as well as with the
second minihelix (residues 64 to 68). Several water molecules
are found near the periphery of the pocket (with B-factors
varying between 19 and 49 Å^2). (c) Interactions between
the first minihelix of hGH (residues 41 to 48) and the
solvent-exposed face of the CC′FG sheet of the N-terminal
domain of the receptor. (d) Interactions between residues on
helix 1 of hGH and loop FG[C] of the receptor. No intermolecular
hydrogen bonds are found; Glu174 of the hormone interacts with
histidine residues 18 and 21.
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