Past exam of the chemistry B course of the University of Cambridge 2024 Paper 2 B10 c Solution 2026-10-20
The zinc ion is coordinated by protein donors and a water oxygen placed near the reacting C6 center. Zinc acts as a Lewis acid that activates and positions water. Its positive charge withdraws electron density from oxygen, lowers the effective p of coordinated water and facilitates formation of the attacking hydroxide, potentially with assistance from a nearby base. The same metal–oxygen interaction can stabilize developing negative charge as the addition intermediate forms. Zinc stays Zn(II); this is metal ion catalysis, not a zinc redox cycle.
The structure identifies a plausible reaction geometry, but a static X-ray model does not by itself establish the water's protonation state, proton-transfer order or the rate-limiting step. Structural work with bound transition-state analogues independently supports a zinc-containing catalytic center.[ref]
Atomic structure of adenosine deaminase complexed with a transition-state analog: understanding catalysis and immunodeficiency mutations by David K. Wilson and others. 1991, pp. 1278–1284, catalytic zinc and the bound transition-state analogue
An appropriate experimental test would compare native enzyme, a metal-depleted preparation and stoichiometrically zinc-reconstituted enzyme, checking retained fold and active enzyme concentration. Loss and recovery of activity with those controls distinguishes a catalytic metal requirement from nonspecific denaturation.