30 Chapter 2
can be appreciated from the 3D picture of the helix (Figure 2.16). This is further characterised by an
approximate 5.4 Å PP separation between adjacent intra-strand phosphorus atoms.
2.2.4 The B-DNA Famil y
The general features of the B-type structure, obtained from DNA fibres at high relative humidity (95% RH)
were first put into sharper focus by X-ray studies on the dodecamer d(CGCGAATTCGCG) and its C-5
bromo-derivative at cytosine-9. The structure of the so-called Dickerson–Drew dodecamer has now been
revealed at atomic resolution.^10 The B-conformation has been observed in crystals of numerous oligomers
and initial standard parameters were averaged from structures of ten isomorphous oligodeoxynucleotides
(Figure 2.17).
In B-form DNA, the base pairs sit directly on the helix axis so that the major and minor grooves are of
similar depth (Table 2.3). Its bases are stacked predominantly above their neighbours in the same strand and
are perpendicular to the helix axis (Table 2.4). The sugars have the C2-endopucker (with some displaying
puckers in the neighbouring ranges of the pseudorotation phase cycle, such as C1-exoor O4-endo), all
the glycosides have the anticonformation, and most of the other rotamers have normal populations (Table
2.5). Adjacent phosphates in the same chain are further apart, P...P6.7 Å, than in A-DNA (Table 2.4).
The interaction of water molecules around a DNA double helix can be very important in stabilising
helix structure,^11 to the extent that hydrationhas sometimes been described as the ‘fourth component’ of
DNA structure, after bases, sugars and phosphates. Just how many water molecules per base pair can be
seen in an X-ray structure depends on the quality of structure resolution. In the best structures, up to 14
unique waters per base pair have been resolved. For B-DNA, whose stability is closely linked to high
humidity (Section 2.3.1), highly ordered water molecules can be seen in both major and minor grooves.
The broad major groove is ‘coated’by a uni-molecular layer of water molecules that interact with exposed
CO, N and NH functions and also extensively solvate the phosphate backbone. The narrow minor
groove contains an inner and an outer zig-zag chain of water molecules that form four regular planar hexa-
gons in the central AT region of the Dickerson–Drew dodecamer (Figure 2.18).^12 The inner spine of
hydrationconsists of alternating water molecules that are buried at the floor of the groove, directly con-
tacting the bases, and located in the second-shell, above and between first-shell water molecules and closer
to the periphery of the groove, respectively.
To a first approximation, the differences between the A, B and other polymorphs of DNA can be described
in terms of just two coordinates: slide (Dy) and roll (). Clearly, A-DNA has high roll and negative slide
Table 2.4 Comparison of helix parameters for A-DNA and B-DNA crystal structures and for a model
Z-DNA helix
- Base step parameters
Helix Step Roll Tilt Cup Slide Twist Rise Dxy Radp
B All 0.6° 0.0° 10.0° 0.4 Å 36.1° 3.36 Å 3.5 Å 9.4 Å
A All 6.3° — — 1. 6Å 31.1° 2. 6Å — 9.5 Å
Z C–G 5.8° 0.0° 12.5° 5.4 Å 9.4° 3.92 Å 5.0 Å 6.3 Å
Z C–G 5.8° 0.0° 12.5° 1.1 Å 50.6° 3.51 Å 6.0 Å 7.3 Å
- Base pair parameters
Base Tip Inclination Propeller Buckle Shift Slide P–PaB All 0.0° 2.4° 11.1° 0.2° 0.8 Å 0.1 Å 8.8–14 Å
A All 11.0° 12.0° 8.3° 2.4° 4.1 Å — 11.5–11.9 Å
Z C 2.9° 6.2° 1.3° 6.2° 3.0 Å 2.3 Å 13.7 Å
ZG 2.9° 6.2° 1.3° 6.2° 3.0 Å 2.3 Å 7.7 Å
aP–P is the shortest inter-strand distance across the minor groove.