---
title: "Aspartyl protease (HIV protease) Template | MolDraw"
url: https://www.moldraw.com/templates/enzyme-hiv-protease/
description: "Aspartyl protease (HIV protease) template: In HIV-1 protease (a C2-symmetric dimer) one Asp25 carboxylate deprotonates a water molecule as it attacks the…"
lang: en
publisher: Scidart Academy
generated: 2026-11-13
---
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# Aspartyl protease (HIV protease) template

![Aspartyl protease (HIV protease) template: In HIV-1 protease (a C2-symmetric dimer) one Asp25 carboxylate deprotonates a water molecule as it attacks the scissile carbonyl and Asp25′–H protonates the carbonyl oxygen, giving a neutral gem-diol; the roles then reverse to protonate the nitrogen and break the C–N bond.](https://www.moldraw.com/templates/enzyme-hiv-protease.webp)

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In HIV-1 protease (a C2-symmetric dimer) one Asp25 carboxylate deprotonates a water molecule as it attacks the scissile carbonyl and Asp25′–H protonates the carbonyl oxygen, giving a neutral gem-diol; the roles then reverse to protonate the nitrogen and break the C–N bond.

## Mechanism step by step

Two Asp25 side chains, one from each subunit, activate water: a tetrahedral gem-diol intermediate, then C–N cleavage

1. **Gem-diol** – Asp25⁻ deprotonates water as it attacks the C=O; Asp25′–H protonates the carbonyl O
2. **C–N cleavage** – Asp25′⁻ takes an OH proton, C=O re-forms, and the N takes H⁺ from Asp25–H as it leaves

## Key points

- HIV protease is a homodimer: each 99-residue subunit gives one Asp25 (Asp-Thr-Gly motif) to the active site (Navia et al. 1989); pepsin and renin are single-chain aspartyl proteases.
- No covalent enzyme intermediate forms; water is the nucleophile, unlike the serine and cysteine proteases.
- Saquinavir, ritonavir and darunavir are transition-state mimics: a non-cleavable hydroxyethylene or hydroxyethylamine replaces the tetrahedral gem-diol.
- The protease cuts the Gag and Gag-Pol polyproteins; blocking it gives immature, non-infectious virions.

Drawn with 72 atoms, 11 arrows, 6 shapes – every one editable in MolDraw.

## Sources

- [Nelson & Cox, Lehninger Principles of Biochemistry, 8th ed., 2021, ch. 6](https://openlibrary.org/isbn/9781319228002) Textbook
- [Berg, Tymoczko, Gatto & Stryer, Biochemistry, 9th ed., 2019, ch. 9](https://openlibrary.org/isbn/9781319114657) Textbook
- [Navia, Fitzgerald, McKeever, Leu, Heimbach, Herber, Sigal, Darke & Springer, Nature 1989, 337, 615](https://doi.org/10.1038/337615a0) Original paper

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