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Figure 3.
Figure 3. Electron density and electrostatic surface of three
ligands m^7GTP, Bn^7GMP and FBn^7GMP bound to eIF4E. (a), (c)
and (e) The F[o]–F[c] electron density (2.5σ) for the ligands
m^7GTP, Bn^7GMP and FBn^7GMP, respectively, in blue, with the
green mesh showing the 2 F[o]–F[c] map for eIF4E (1.2σ) and
the structured waters. Incorporation of the bulky benzyl group
in Bn^7GMP and FBn^7GMP causes the W102 side-chain to flip
180°. The m^7G moiety of the cap analogue forms the same
hydrogen bonds (shown in yellow) with the E103 side-chain and
the amide backbone of W102. (b), (d) and (f) The electrostatic
potential of the eIF4E surface. The phosphate-binding region has
a distinctive positive charge whilst the pocket in which the
m^7G moiety intercalates is more hydrophobic in nature. The m^7G
moiety forms a parallel stack with W102 and W56 and interacts
with the two ring systems via cation–π interactions.
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