Past exam of the chemistry B course of the University of Cambridge / 2024 / Paper 1 / B5 / b

Use the standard Watson–Crick edges, with the glycosidic attachments at purine N9 and pyrimidine N1. The A–T pair has two hydrogen bonds: adenine N6–H donates to thymine O4, and thymine N3–H donates to adenine N1. The C–G pair has three: cytosine N4–H donates to guanine O6, guanine N1–H donates to cytosine N3, and guanine N2–H donates to cytosine O2. The middle and right panels above show these atoms and the sugar-attachment directions.

The major-groove side is the edge toward purine N7 and toward thymine O4/its methyl group or cytosine N4. The minor-groove side is toward purine N3 and adenine C2–H or guanine N2, and toward pyrimidine O2 and the sugar attachments. Groove labels refer to the exposed outer edges of the paired bases; the hydrogen bonds joining the bases are not themselves empty grooves. The resulting patterns differ even when the bases remain paired inside duplex DNA.

At ordinary physiological pH, the arginine side chain is predominantly guanidinium. Its N–H groups are donors, and its positive charge can reinforce favorable electrostatic interactions. guanine exposes adjacent O6 and N7 acceptors in the major groove, allowing two guanidinium N–H donors to make a paired interaction without breaking Watson–Crick pairing. The diagram places this arginine contact on the exposed guanine edge, not between the paired bases.

adenine also exposes N7, but at the corresponding neighboring position it has the exocyclic N6 amino donor rather than a carbonyl acceptor. It therefore cannot make the same donor-to-two-acceptors match with guanidinium. A single N7 contact would be less discriminating. The classic structural recognition analysis explicitly proposed paired arginine–guanine contacts in the major groove.^[ref] protein geometry, hydration and phosphate contacts also affect sequence recognition; this local motif explains a preference rather than guaranteeing that every arginine-containing protein recognizes every G–C site.