Watson-Crick purine-pyrimidine base

Fig. 1. Elements of DNA. stricture (a) a deoxypolynucleotide chain, which reads d(ACTG) from 3 — 5 or d(GTCA) from 3 — 5 and (b) and (c) the Watson-Crick purine-pyrimidine base pairs, A-T and G-C. respectively, where—s represents aliachinenl lo the deoxyribose...

The N-H- -N bonds constitute about a quarter of the hydrogen bonds in the purine and pyrimidine crystal structures (see Thble 7.14). The proportion is much smaller in the nucleosides and nucleotides Thble 7.12, where they compete with the stronger O-H- -O and N-H- -O interactions. In combination with N - H O=C, the N - H N bonds form the Watson-Crick and related base-pair configurations in purine and pyrimidine crystal structures, and in the oligonucleotides and nucleic acids. 

The discovery of these base pairs, which imply the double helical structure of DNA, stimulated a series of crystal structural studies not only of complexes of purines and pyrimidines, but of other complexes involving related molecules and their derivatives. Although we can formulate a large number of possible heterocombinations in matrix form, as shown below these complexes are reluctant to crystallize even when there is spectroscopic evidence of hetero-complex formation in solution. This is presumably because self-(homo)-association is energetically more favorable and only in rare cases were crystals of hetero complexes actually formed. Because of their three hydrogen bonds, G-C complexes form and crystallize more readily. There have been many attempts to crystallize the Watson-Crick A-U base pair, but none was successful and it only formed when the dinucleoside phosphate adenylyl-3,5,-uridine (ApU [536]) or higher oligomers were crystallized (see Part III, Chapter 20). 

As in the homo-base pair series, most hetero-base pair associations involve two hydrogen bonds. Only the Watson-Crick G-C base pair and two guanine-uracil pairs of no biological importance form three hydrogen bonds. In the following, we summarize the possible base-base combinations in matrix notation, with those possible with nucleic acids [where pyrimidine N(l) and purine N(9) are substituted] indicated in italic letters, as before. 

Under physiological conditions DNA exists predominantly as a duplex formed between complementary anti-parallel strands of DNA in which the purines of one strand are hydrogen bonded to the pyrimidines of the complementary strand and vice versa to form G C and A T base pairs. The Watson-Crick G C base pairs (Figure 2) possess three hydrogen bonds and the A T base pairs two hydrogen bonds, each hydrogen bond contributing approximately 2 kcal mol to the stabil-... 

TABLE 12.9 Electron Affinities (in eV) of Purines and Pyrimidines and Watson Crick Hydrogen-Bonded Base Pairs... 

Finally, the third application concerns the problem of tautomeric shifts in the purines and the pyrimidines and is of fundamental significance in relation to the mechanism of mutagenesis, in particular through the mis-pairings of bases. The essential observation in this field is that in the usual Watson-Crick pairing the bases are in their lactam and amino forms which... 

Figure 3. Purine-pyrimidine base-pairing structures as found in DNA (Watson-Crick configurations).

This is consistent with there not being enough space (20 °) for two purines to fit within the helix and too much space for two pyrimidines to get close enough to each other to form hydrogen bonds between them. These relationships are often called the rules of Watson-Crick base pairing. 

The DNA double heUx illustrates the contribution of multiple forces to the structure of biomolecules. While each individual DNA strand is held together by covalent bonds, the two strands of the helix are held together exclusively by noncovalent interactions. These noncovalent interactions include hydrogen bonds between nucleotide bases (Watson-Crick base pairing) and van der Waals interactions between the stacked purine and pyrimidine bases. The hehx presents the charged phosphate groups and polar ribose sugars of... 

The formation of three-stranded nucleic acid complexes was first demonstrated over five decades ago [56] but the possible biological role of an extended triplex was expanded by the discovery of the H-DNA structure in natural DNA samples [57-59]. H-DNA is an intermolecular triplex that is generally of the pyrimidine-purine x pyrimidine type ( dot -Watson-Crick pairing and cross Hoogsteen base paring) and can be formed at mirror repeat sequences in supercoiled plasmids [59]. 

Figure 5-6 Outlines of the purine and pyrimidine bases of nucleic acids showing van der Waals contact surfaces and some of the possible directions in which hydrogen bonds may be formed. Large arrows indicate the hydrogen bonds present in the Watson-Crick base pairs. Smaller arrows indicate other hydrogen bonding possibilities. The directions of the green arrows are from a suitable hydrogen atom in the base toward an electron pair that serves as a hydrogen acceptor. This direction is opposite to that in the first edition of this book to reflect current usage.

DNA polymerases have just one binding site for all four combinations of base pairing—AT, TA, GC, and CG. The specificity of these sites is dictated by the Watson-Crick pairing rules, in that the sites themselves appear to recognize just the overall shape of a correct purine-pyrimidine pair, with the precise specificity resulting from the complementary nature of the base pairing. The polymerase catalyzes the transfer of a complementary deoxynucleoside monophosphate from its triphosphate to the 3 -hydroxyl of the primer terminus (equation 14.1). 

An even more remarkable prediction was made by Crick and Watson (1953) of the structure of the vast molecules, such as that of deoxyribonucleic acid (DNA), which are concerned with the maintenance and transference of genetic information. These molecules contain very long chains of nucleotide units linked by covalency bonds. (A nucleotide consists of the residue of a sugar, often ribose or deoxyribose, one of a purine or pyrimidine base, and one of phosphoric acid, bonded together.) The Crick-Watson hypothesis was that the macromolecule consists of two such chains,... 

In agreement with the chemomimetic concept as defined by Eschen-moser, the panel of enzymatic transformations for the biosynthesis of purines that we currently observe in the cell can be hypothesized to have evolved from primitive chemical processes [48-50]. 2-Carbonitrile and 2-carboxamide AICA and AICN derivatives, respectively, were also used as intermediates for the synthesis of adenine 1 and 8-substituted adenines 7 and 8 [51]. In principle, purine derivatives 7 and 8 may pair with pyrimidine bases by formation of Watson-Crick or Hoogsteen hydrogen bond interactions. 

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