MOLECULAR STRUCTURE OF NUCLEIC ACIDS
A Structure for Deoxyribonucleic Acid
We suggest a structure for the salt of deoxyribonucleic acid (DNA .). This structure has novel features which are of considerable biological interest.
A structure for nucleic acid has been proposed by Pauling and Corey (1). Have kindly put at our disposal the manuscript before publication. Their model consists of three intertwined chains, with phosphates near the axis of the fiber, and the bases out. In our opinion, this structure is unsatisfactory for two reasons: (1) believe that the material obtained the X-ray diagrams is the salt, not the free acid. Without the acidic hydrogen atoms is not clear what forces can 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 triple chain structure has been suggested by Fraser (in press). In his model the phosphates are out and the bases inward, held together by hydrogen bonds. This structure thus described is rather ill-defined as not discussed.
We offer here a radically different structure for the salt deoxyribonucleic acid. This structure has two helical chains each lap around the same axis (see diagram). We made the usual chemical assumptions, specifically, that each chain consists of phosphate diester groups joining beta-D residues desoxirribofuranosa links-3 ', 5'. The two chains (but not their bases) are related by a dyad perpendicular to the axis of the fiber. Both chains follow right-handed helix, but due to the dyad the sequences of atoms in the two chains run in opposite directions. Each of the chains separate model resembles Furberg No. 1 (2), that is, the bases are on the inside of the loop and phosphates on the outside. The configuration of the sugar and the atoms near approaches to the "standard configuration" of Furberg, sugar is available at right angles to the base attached. There is a residue on each chain every 3.4 Å in the direction-z. We have assumed an angle of 36 degrees between adjacent residues in the same chain, so that the structure is repeated after 10 residues on each chain, ie after 34 Å. The distance of a phosphorus atom from the axis of the fiber is 10 Å. As the phosphates are on the outside, cations have easy access to them. The structure is open and the water content is rather high. For us, content low bases and the structure would approach would be more compact.
The novel aspect of the structure is the manner in which the two chains are held together by purine and pyrimidine bases. The planes of the bases are perpendicular to the axis of the fiber. They meet in pairs, a base of one of the chains connected by hydrogen bonds to a base of the other chain, and thus the two are joined side by side with identical z-coordinate One of the pair must be purine and one pyrimidine. Hydrogen bonds are as follows: purine position 1 to pyrimidine position 1; purine position 6 to pyrimidine position 6 [etc.]
This figure is purely schematic. The two ribbons symbolize the sugar-phosphate chains, and the horizontal rods the pairs of bases holding the chains together. The vertical line marks the axis of the fiber.
Assuming that the bases only occur within the structure in the most plausible tautomeric forms (that is, setting the keto rather than enol) are the specific pairs of bases can join. These pairs are: adenine (purine) with thymine (pyrimidine) and guanine (purine) with cytosine (pyrimidine).
In other words, if an adenine is a member of a couple, on a string, then the other member must be thymine; something similar happens for the guanine and cytosine. The sequence of bases on a single chain does not appear to be restricted in any way. However, if they can only form specific base pairs, it follows that knowing the sequence of bases on one strand, then the sequence on the other chain is automatically determined.
has been found experimentally (3.4) that the ratio of adenine to thymine, and the ratio of guanine to cytosine, are always very close to unity for deoxyribonucleic acid. It is probably impossible to build this structure with a ribose sugar instead of deoxyribose, the extra oxygen atom would make too closed and form a van der Waals bond.
The X-ray data previously published (5.6) on deoxyribonucleic acid are insufficient for a rigorous test of our structure. So far we can say is roughly compatible with the experimental data, but should be seen as unproven until you have verified with more accurate results. Some of these will be submitted on the following communications. We were not aware of the details of the results presented when we devised our structure, which rests mainly but not entirely on published and experimental data and stereochemical arguments.
not escaped our communication pairing específico que hemos postulado sugiere inmediatamente un mecanismo copiador para el material genético .
Todos los detalles de la estructura, incluyendo las condiciones presumidas para su construcción, junto con un conjunto de coordenadas para los átomos, se publicarán con posterioridad.
Estamos en deuda con el Dr. Jerry Donohue por las constantes críticas y consejos, especialmente sobre distancias interatómicas. También hemos sido estimulados por el conocimiento general de la naturaleza y los resultados experimentales inéditos así como ideas del Dr. M.H.F. Wilkins , la Dra. R.E. Franklin y sus colaboradores del King's College , en Londres. Uno Whom (JDW) has been funded by a grant from the National Foundation for infantile paralysis.
JD Watson FHC Crick
Medical Research Council Unit for the Study of the Structure Molecular Biological Systems
Cavendish Laboratory, Cambridge
April 2 (1) Pauling, L. and Corey, RB, Nature, 171, 346 (1953); Proc.USNat.Sci., 39, 84 (1953).
(2) Furberg, S. Minutes Chem.Scand., 6, 634 (1952).
(3) Chargaff, e. For reference see Zamenhof, S, Brawerman, G. and Chargaff, E., Biochem. et. Biophys. Ata, 9, 402 (1952).
(4) Wyatt, GR, J. Gen.Physiol., 36, 201 (1952).
(5) Astbury, WT, Symp.Soc.Exp.Biol. 1, Nucleic Acid, 66 (Cambridge University Press, 1947).
(6) Wilkins, MHF and Randall, JT, Biochim. et Biophys. Acta, 10, 192 (1953).
Article published in the journal Nature , April 25, 1953, p. 737.
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