Chemistry Reference
In-Depth Information
Crystals of d(TG
4
T) were also formed from a solution that contained both NaCl
and CaCl
2
.
157
As in many other nucleic acid crystals divalent Ca
2+
ions were found
at crystal lattice contact points between nucleic acid assemblies (i.e. bridging between
backbone phosphates of two G-quadruplexes). Single water molecules were found
to provide a fi fth oxygen atom for coordination of the outermost Na
+
ions that are
coordinated in the planes of the terminal G-quartets. Additionally, water molecules
were found along the phosphate backbone, in the four grooves, and as part of the
hydration shell of Ca
2+
ions. There was no evidence that Ca
2+
ions substituted for
Na
+
ions at any sites within the G-quadruplex. Crystallization from a solution con-
taining MgCl
2
resulted in no bound divalent cations.
246
An earlier study established
a single Mg
2+
ion located at the surface of the quadruplex.
247
In the recent crystallographic study
139
on d(TG
4
T) a new crystal form for the
tetramolecular quadruplex with four parallel strands has been found (PDB ID
2GW0). In these crystals, formed in a mixed Ca
2+
and Na
+
ion environment, the
channel along the central cavity of the quadruplex dimer is populated by cations in
an asymmetric way (Figure 3.8c). One half has three Na
+
ions, whereas the other
half has three Ca
2+
ions. The ion channel is capped by water molecules. Na
+
ions are
irregularly positioned with respect to the G-quartet planes. The outermost Na
+
is
almost coplanar with a G-quartet, whereas the inner one is almost equidistant from
two G - quartets. A Ca
2+
ion sits at the dimer interface (itself in plane with four other
Ca
2+
ions each in a groove). Two Ca
2+
ions are approximately midway between
G - quartets.
139
d(TG
4
T) has been found to produce two distinct crystal forms when crystallized
from solutions containing both Na
+
and Tl
+
ions.
247
The quality and resolution of
data (i.e. 2.2 and 2.5 Å) combined with the very different electron densities of Tl
+
and Na
+
ions allowed these two cations to be distinguished in the G-quadruplex
structure. One crystal form contained two G-quadruplexes in the asymmetric unit
(PDB ID 1S45), whereas the other form contained three G-quadruplexes (PDB ID
1S47). In all cases, G-quadruplexes are stacked in a head-to-head fashion with a 5
′
orientation, as found in the Na
+
crystal structure.
157
The main difference lies in
the position of metal ions within the G-quadruplex and the low occupancy of inner-
G-quadruplex cation coordination sites by Tl
+
ions (i.e. occupancy levels between
0.15 and 0.70). The Tl
+
ions coordinated within the G-quadruplex are positioned
between two neighbouring G-quartet planes (Figures 3.8d-e).
247
This coordination
geometry would be expected for Tl
+
ions, as the ionic radius of Tl
+
(1.44 Å ) is slightly
larger than that of K
+
and certainly too large to be coordinated within the plane of
a G - quartet. Low Tl
+
ion occupancy has been attributed to the higher concentration
of Na
+
ions in the crystallization solution.
247
The tilt of G-quartets towards the 5
to 5
′
- end
junction has been observed in the Tl
+
- containing structure with one dimer (PDB ID
1S45), and with one dimer and one monomer (PDB ID 1S47).
247
It has been appreciated for some time that Sr
2+
ions can promote G-quadruplex
formation.
130
The fact that Sr
2+
ions can stabilize G-quadruplexes to a similar degree
as K
+
seemed somewhat enigmatic. The ionic radius of Sr
2+
(1.13 Å ) is in between
that of Na
+
and K
+
, however the energy from electrostatic repulsions between
Sr
2+
ions within a G-quadruplex would be four times that of monovalent cations,
if Sr
2+
ions were coordinated with a similar spacing along the central axis of a
′
