---
title: "Carbonic anhydrase Template – Chemistry Diagram | MolDraw"
url: https://www.moldraw.com/templates/enzyme-carbonic-anhydrase/
description: "Carbonic anhydrase template: In carbonic anhydrase II, OH⁻ on Zn²⁺ (held by His94, His96, His119) attacks CO₂ to give Zn-bound HCO₃⁻, which water displaces…"
lang: en
publisher: Scidart Academy
generated: 2026-11-13
---
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# Carbonic anhydrase template

![Carbonic anhydrase template: In carbonic anhydrase II, OH⁻ on Zn²⁺ (held by His94, His96, His119) attacks CO₂ to give Zn-bound HCO₃⁻, which water displaces; the Zn-bound water (pKa ≈ 7) is deprotonated through His64 to regenerate Zn²⁺–OH⁻.](https://www.moldraw.com/templates/enzyme-carbonic-anhydrase.webp)

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In carbonic anhydrase II, OH⁻ on Zn²⁺ (held by His94, His96, His119) attacks CO₂ to give Zn-bound HCO₃⁻, which water displaces; the Zn-bound water (pKa ≈ 7) is deprotonated through His64 to regenerate Zn²⁺–OH⁻.

## Mechanism step by step

Zn²⁺-bound hydroxide attacks CO₂; bicarbonate is replaced by water, and His64 shuttles the proton out

1. **OH⁻ attacks CO₂** – Zn²⁺–OH⁻ adds to the carbon of CO₂ bound in a hydrophobic pocket
2. **Water replaces HCO₃⁻** – HCO₃⁻ leaves the zinc; water binds in its place (ligand exchange)
3. **Proton shuttle** – His64 takes H⁺ from Zn²⁺–OH₂ through a chain of waters (rate-limiting)
4. **To the buffer** – His64–H⁺ hands the proton to buffer outside the active site

## Key points

- Zn²⁺ lowers the pKa of bound water from about 15.7 to about 7, giving a hydroxide nucleophile at neutral pH.
- kcat ≈ 10⁶ s⁻¹ (CA II), among the fastest enzymes; kcat/KM approaches the diffusion limit.
- The rate-limiting step is proton transfer: His64 swings between "in" and "out" to pass H⁺ to buffer (the His64Ala mutant is rescued by imidazole buffers).
- Sulfonamides such as acetazolamide bind to the zinc and inhibit the enzyme (glaucoma, altitude sickness).

Drawn with 65 atoms, 11 arrows, 8 shapes – every one editable in MolDraw.

## Sources

- [Berg, Tymoczko, Gatto & Stryer, Biochemistry, 9th ed., 2019, ch. 9](https://openlibrary.org/isbn/9781319114657) Textbook
- [Lindskog, Pharmacol. Ther. 1997, 74, 1](https://doi.org/10.1016/s0163-7258(96)00198-2) Review
- [Tu, Silverman, Forsman, Jonsson & Lindskog, Biochemistry 1989, 28, 7913](https://doi.org/10.1021/bi00445a054) Original paper

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