Figure 2.

Proposed role of His²⁵⁷ in formation of the transition state, featuring dynamic compression of the O5′–O4′–O_P “oxygen stack”. The “oxygen stack” is represented by hashed bonds connecting bolded atoms, and arrows indicate promoting vibrational modes. Dashed bonds represent hydrogen bonds or partial bonds. Dynamic motion in the enzyme active site pushes O-5′ and the phosphate oxygen towards the ring oxygen, leading to increased electron density in the center of reactivity. This contributes electron density to weaken the N9–C1′ bond, enhances hypoxanthine’s leaving group ability, and forms the developing ribooxacarbenium ion.