《watsoncrick1953年发表nature.pdf》由会员分享，可在线阅读，更多相关《watsoncrick1953年发表nature.pdf（2页珍藏版）》请在三一文库上搜索。
1、Am J Psychiatry 160:4, April 2003623 Commemorations http:/ajp.psychiatryonline.org MOLECULAR STRUCTURE OF NUCLEIC ACIDS A Structure for Deoxyribose Nucleic Acid We wish to suggest a structure for the salt of deoxyribose nucleic acid (D.N.A.). This structure has novel features which are of considerab
2、le biological interest. A structure for nucleic acid has already been proposed by Pauling and Corey (1). 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 outsid
3、e. In our opinion, this structure is unsatisfactory for two reasons: 1) We believe that the material which gives the X-ray dia- grams 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
4、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
5、. This structure as described is rather ill-defined, and for this reason we shall not comment on it. 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
6、usual chem- ical assumptions, namely, that each chain consists of phosphate diester groups joining -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 dy
7、ad the sequences of the atoms in the two chains run in opposite directions. Each chain loosely resembles Furbergs (2) model No. 1; that is, the bases are on the inside of the helix and the phosphates on the outside. The con- figuration of the sugar and the atoms near it is close to Furbergs standard
8、 configuration, the sugar being roughly perpendicular to the attached base. There is a residue on each chain 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
9、. 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 struc- ture could become
10、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 hydrogen-bonded to a single
11、base from the other chain, so that the two lie side by side with identical z- co-ordinates. 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 posi- tio
12、n 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 (pyrim- idine), and gua
13、nine (purine) with cytosine (pyrimidine). In other words, if an adenine forms one member of a pair, on either chain, then on these assump- tions 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.
14、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. This figure is purely diagram- matic. The two ribbons sym- bolize the two phosphate sugar chains, and the horizon-
15、 tal rods the pairs of bases holding the chains together. The vertical line marks the fi- bre axis. 624Am J Psychiatry 160:4, April 2003 COMMEMORATIONS http:/ajp.psychiatryonline.org It has been found experimentally (3, 4) that the ratio of the amounts of adenine to thymine, and the ratio of guanine
16、 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 data (5, 6) on deoxyribo
17、se 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 communica- tions. We w
18、ere 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 argu- ments. It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible
19、copying mechanism for the genetic material. Full details of the structure, including the conditions assumed in building it, together with a set of co-ordinates for the atoms, will be published elsewhere. We are much indebted to Dr. Jerry Donohue for constant advice and criticism, especially on inter
20、atomic 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 Kings College, London. One of us (J.D.W.) has been aided by a fellowship from the National Foundation
21、 for Infantile Paralysis. References 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
22、, 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). J.D. WATSON F.H.C. CRICK Medical Research Council Unit for the Study of the Molecular Structure of Biological Systems, Cavendish Laboratory, Cambridge. April 2. Reprinted by permission from Nature vol. 171:737-738 (1953). Copyright 2003 Macmillan Publishers Ltd.