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Tuesday, July 17, 2007

Nucleotides Can Adopt Many Different Conformations

Individual nucleotides in solution can adopt many different conformations. For example, the deoxyribose sugars can bend and twist in many different ways. Two of the most stable conformations are shown on the left. They are the conformations found in some DNA structures.

The C-2′ endo conformation (top) allows the maximum separation between the oxygen atoms at the 5′ and 3′ positions. What this means is that any polynucleotide strand with sugars in this conformation will be extended. On the other hand, strands and helices with sugars in the C-3′ endo conformation will be much more compact with tighter helices.

If you look at all of the bonds that make up the sugar-phosphate backbone of a polynucleotide strand you will see that there are a lot of possible conformations. You can have free rotations around many of these bonds. Now, as it turns out, the structure of double-stranded DNA has a well-defined conformation where many of these bond angles are fixed but if you were handed two strands of DNA you would be hard pressed to bend them into the proper conformation of real DNA.

This is one of the reasons why it was so hard to predict the structure of DNA even though the chemical structure of the polynucleotides was known.

In addition to sugar puckers and bond rotations around the backbone, there are also many conformations of the base relative to the sugar. The two extreme conformations involve rotation around the β-N- glycosidic bond shown in green in the figures below. In the anti- conformation (left) the base is rotated so that it is as far from the sugar as possible. This is the most stable conformation and it's found in most DNAs. In the syn conformation (right) the base is rotated so that it's over the sugar leading to a much more compact structure.

When the structure of double-stranded DNA was being worked out, the conformations of the nucleotides were not known. It wasn't even obvious that the more stable anti conformation of free nucleotides would necessarily be the conformation in DNA. You can see that attempts to build a model of DNA without lots of additional information were doomed to failure. Several people tried and failed, including the greatest chemist of the day Linus Pauling.

©Laurence A. Moran 2007
[Figures are from Moran/Scrimgeour et al. Biochemistry 2nd ed. (1994) ©Neil Patterson Publishers/Prentice Hall.]

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