Pyrimidine bases hydrogen-bonding possibilities

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.

Hydrogen bonds are not just important for small molecules. Duplex strands of DNA and RNA are held together by hydrogen bonds between complementary purine and pyrimidine bases. Because each individual bond is weak it is possible to unzip these large molecules and use the primary sequence in transcription (for sequence copying) or translation (for protein synthesis) and zip up the hydrogen bonds after the information has been accessed by transcription and translation enzymes. Transfer of encoded information can therefore occur without destroying the sequences of the parent compound. 

The chemical properties of the purine and pyrimidine bases include highly conjugated double bond systems within the ring structures. For this reason, nucleic acids have a very strong absorption maximum at about 260 nm, which is used for nucleic acid quantitation. Moreover, the bases can exist in two tautomeric forms, the keto and enol forms (Figure 10.2). In DNA and RNA, the keto forms are by far the more predominant, and this property makes it possible for the bases to form intermolecular hydrogen bonds (see Figure 10.18). 

Some of the hydrogen-bonded dimer configurations described in the matrices are observed in the crystal structures of the purines and pyrimidines, but this is by no means the general rule. This may be because the number of crystal structures in which self-base pairing occurs is relatively small compared with the number of possibilities. Certain arrangements appear to be particularly favored for reasons... 

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. 

There is a large variability possible in the structures of double stranded DNA due to the fact that (compared to polypeptides) many more bonds can be rotated in the backbone of each monomer (Scheme 14). The most common and physiologically most important structure is the B-DNA helix. It consists of two polynucleotide chains running in opposite direction which coil around a common axis to form a right-handed double helix. In the helix, the phosphate and deoxyribose units of each strand are on the outside, and the purine and pyrimidine bases on the inside. The purine and pyrimidine bases are paired by selective hydrogen bonds adenine is paired with thymine, and guanine with cytosine (Scheme 15). The structure is very flexible and can form a supercoil with itself, or around proteins. It can form a left-handed supercoil around histones to form nucleosomes which assemble in yet another helical structure to form chromatin. ... 

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