Chemistry Reference
In-Depth Information
The width of the grooves is not constant, but is found to be sequence-
dependent. Alternative models have been presented to provide explanations for this
sequence-dependent variation. NMR spectroscopic analyses of a series of DNA
duplexes have shown that alternating (AT)
n
sequences are characterized by a rather
wide minor groove.
56,57
From a number of experimental and theoretical studies, it
has been concluded that on average the minor groove of DNA A-tracts (several
consecutive adenine residues) is signifi cantly narrower than the minor groove of
G - tracts.
58 - 60
1.5.2 Monovalent Cations
In the report of the fi rst X-ray structure of a double-helical DNA duplex,
[d(CGCGAATTCGCG)]
2
, published by Dickerson and Drew,
58
it was proposed
that a 'spine of hydration', composed of localized, geometrically arranged water
molecules, in the minor groove, is an important structural component of A-tract
DNA. However, this result is not fully conclusive since Na
+
and H
2
O, being isoelec-
tronic, are not easily distinguishable by X-ray diffraction. Egli and coworkers
repeated the structural analyses of the same duplex using X-ray diffraction data to
near-atomic resolution with crystals grown in the presence of Rb
+
cacodylate.
61
They
found that a single Rb
+
ion, with partial occupancy, was localized at the central ApT
step at the bottom of the AATT minor groove (Figure 1.12). The ion replaces the
water molecules that link the keto oxygen of thymines from opposite strands.
The authors suggest that minor groove ion coordination appears to be an iso-
lated event, highly sequence-dependent and unlikely to signifi cantly affect the par-
ticular geometry of the A-tract in the Dickerson-Drew dodecamer. Further studies
by Williams and coworkers on the same duplex using Tl
+
to mimic K
+
showed that
none of the observed Tl
+
sites surrounding the duplex were fully occupied.
62
The
Figure 1.12
Coordination of Rb
+
at the central ApT step in the Dickerson-Drew Duplex.
61
(Reprinted from
Chem. Biol.
,
9
, 3, M. Egli, DNA-cation interactions: Quo vadis?, 10.
Copyright 2002, with permission from Elsevier.)
