reprinted with permission from Nature
A Structure for Deoxyribose Nucleic Acid
April 25, 1953, Nature, Vol. 171, page 737
WE
wish to suggest a structure for the salt of deoxyribose nucleic acid (D.N.A.).
This structure has novel features which are of considerable biological
interest.
A structure for nucleic
acid has already been proposed by Pauling
and Corey1.
They kindly made their manuscript available to us in advance of publication.
Their model consists of three intertwined chains, with the phosphates
near the fibre axis, and the bases on the outside. In our opinion, this
structure is unsatisfactory for two reasons: (1) We believe that the material
which gives the X-ray diagrams is the salt, not the free acid. Without
the acidic hydrogen atoms it is not clear what forces would hold the structure
together, especially as the negatively charged phosphates near the axis
will repel each other. (2) Some of the van der Waals distances appear
to be too small.
Another three-chain
structure has also been suggested by Fraser (in the press). In his model
the phosphates are on the outside and the bases on the inside, linked
together by hydrogen bonds. This structure as described is rather ill-defined,
and for this reason we shall not comment on it.
 |
 |
| This figure is purely diagrammatic. The two ribbons symbolize the two phophate-sugar chains, and the horizonal rods the pairs of bases holding the chains together. The vertical line marks the fibre axis. | |
We wish to put forward a radically
different structure for the salt of deoxyribose nucleic acid. This
structure has two helical chains each coiled round the same axis (see
diagram). We have made the usual chemical assumptions, namely, that each
chain consists of phosphate diester groups joining beta-D-deoxyribofuranose
residues with 3',5' linkages. The two chains (but not their bases) are
related by a dyad perpendicular to the fibre axis. Both chains follow
right-handed helices, but owing to the dyad the sequences of the atoms
in the two chains run in
opposite directions. Each chain loosely resembles Furberg's2
model No. 1; that is, the
bases are on the inside of the helix and the phosphates on the outside.
The configuration of the sugar and the atoms near it is close to Furberg's
"standard configuration," the sugar being roughly perpendicular
to the attached base. There is a residue on each every 3.4 A. in the z-direction.
We have assumed an angle of 36° between adjacent residues in the same
chain, so that the structure repeats after 10 residues on each chain,
that is, after 34 A. The distance of a phosphorus atom from the fibre
axis is 10 A. As the phosphates are on the outside, cations have easy
access to them.
The structure is an open one, and its water content is rather high. At
lower water contents we would expect the bases to tilt so that the structure
could become more compact.
The novel feature of the structure is the manner in which the two chains
are held together by the purine and pyrimidine bases. The planes of the
bases are perpendicular to the fibre axis. They are joined together in
pairs, a single base from one chain being hydroden-bonded to a single
base from the other chain, so that the two lie side by side with identical
z-coordinates. One of the pair must be a purine and the other
a pyrimidine for bonding to occur. The hydrogen bonds are made as follows:
purine position 1 to pyrimidine position 1; purine position 6 to pyrimidine
position 6.
If it is assumed that the
bases only occur in the structure in the most plausible tautomeric forms
(that is, with the keto rather than the enol configurations) it is found
that only specific pairs of bases can bond together. These
pairs are: adenine (purine) with thymine (pyrimidine), and guanine (purine)
with cytosine (pyrimidine).
In other words, if an adenine forms one member of a pair, on either chain,
then on these assumptions the other member must be thymine; similarly
for guanine and cytosine. The sequence of bases on a single chain does
not appear to be restricted in any way. However, if only specific pairs
of bases can be formed, it follows that if the sequence of bases on one
chain is given, then the sequence on the other chain is automatically
determined.
It has been found experimentally3,4
that the ratio of the amounts of adenine to thymine, and the ratio of
guanine to cytosine, are always very close to unity for deoxyribose nucleic
acid.
It is probably impossible to build this structure with a ribose sugar
in place of the deoxyribose, as the extra oxygen atom would make too close
a van der Waals contact.
The previously published X-ray data5,6
on deoxyribose nucleic acid are insufficient for a rigorous test of our
structure. So far as we can tell, it is roughly compatible with the experimental
data, but it must be regarded as unproved until it has been checked against
more exact results. Some of these
are given in the following communications. We were not
aware of the details of the results presented there when we devised our
structure, which rests mainly though not entirely on published experimental
data and stereochemical arguments.
It
has not escaped our notice that the specific pairing we have postulated
immediately suggests a possible copying mechanism for the genetic material.
Full details of the
structure, including the conditions assumed in building it, together with
a set of coordinates for the atoms, will
be published elsewhere.
We are much indebted
to Dr. Jerry Donohue for constant advice and criticism, especially on
interatomic distances. We have also been stimulated by a knowledge of
the general nature of the unpublished experimental results and ideas of
Dr. M. H. F. Wilkins, Dr. R. E. Franklin and their co-workers at King’s
College, London. One of us (J. D. W.) has been aided by a fellowship from
the National Foundation for Infantile Paralysis.
1
Pauling, L., and Corey, R. B., Nature, 171, 346 (1953); Proc.
U.S. Nat. Acad. Sci., 39, 84 (1953).
2
Furberg, S., Acta Chem. Scand., 6, 634 (1952).
3
Chargaff, E., for references see Zamenhof, S., Brawerman, G., and Chargaff,
E., Biochim. et Biophys. Acta, 9, 402 (1952).
4
Wyatt, G. R., J. Gen. Physiol., 36, 201 (1952).
5
Astbury, W. T., Symp. Soc. Exp. Biol. 1, Nucleic Acid, 66 (Camb. Univ.
Press, 1947).
6
Wilkins, M. H. F., and Randall, J. T., Biochim. et Biophys. Acta,
10, 192 (1953).
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