Department of Biology, Massachusetts Institute of Technology, Cambridge 02139.
Proc Natl Acad Sci U S A 84: 8385-9 (1987)
Abstract
The crystal structures of d(CGCA3T3GCG) complex to the antitumor drug
distamycin and the DNA fragment alone were solved by x-ray diffraction
at 2.2 and 2.5 A resolution, respectively. The drug lies in the narrow
minor groove near the center of the B-DNA fragment covering 5 of the 6
A.T base pairs. It is bound to the DNA by hydrogen bonding, van der
Waals, and electrostatic interactions. In addition, the DNA was found to
have an unusual conformation in the (dA)3.(dT)3 regions. These base
pairs have a high positive propeller twist so that in the major groove
the adenine amino group is located intermediate between the carbonyl O-4
groups of two adjacent thymines of the opposite strand, making
bifurcated hydrogen bonds to the two thymine residues. This suggests a
model to explain the unusual properties of poly-(dA).poly(dT) in which a
modified B conformation is associated with a large propeller twist of
the bases and a set of continuous bifurcating hydrogen bonds along the
major groove, which may provide incremental stability to these segments.
In addition, shorter segments of (dA)3-6.(dT)3-6 may have this
conformation in the midst of B-DNA and stabilize bends in the DNA that
may be associated with stacking on one of the high propeller-twisted
bases at the ends of these segments.
Mesh Headings
Unique Identifier: 88068599