Obligate homodimer where each subunit contributes one Asp25 to a shared catalytic dyad. Hydrolyses viral polyproteins into functional proteins — essential for HIV maturation.
The flexible β-hairpin "flaps" (residues 43–58 on each chain) gate access to the active site. Flap opening/closing is the slow conformational step and the target of all clinical protease inhibitors, which trap the closed conformation.
The β-hairpin flaps (residues 43–58 on each protomer) are in an open/semi-open state in the apo enzyme. Substrate enters the active-site cleft, sliding past the flap tips (Ile50/Ile50').
| Substrate | kcat (s⁻¹) | KM (mM) | kcat/KM (M⁻¹s⁻¹) | pH | T (°C) | Source |
|---|---|---|---|---|---|---|
| H-Lys-Ala-Arg-Val-Nle-Phe(pNO2)-Glu-Ala-Nle-NH2 (chromogenic) | 5.60 | 0.036 | 1.56 × 10⁵ | 5.6 | 37 | Richards et al., FEBS Lett 1990 |
| Ac-Ser-Gln-Asn-Tyr-Pro-Ile-Val-NH2 (MA/CA site mimic) | 8.10 | 0.13 | 6.20 × 10⁴ | 5.5 | 37 | Tözsér et al., FEBS Lett 1991 |
Integrate the reaction v = Vmax·[S] / (Km,app + [S]) in closed form with RK4, across any [S], [E], and an optional reversible inhibitor. Defaults are drawn from the curated kinetic record for this enzyme where available.
Defaults seeded from H-Lys-Ala-Arg-Val-Nle-Phe(pNO2)-Glu-Ala-Nle-NH2 (chromogenic) at pH 5.6 / 37 °C — source: Richards et al., FEBS Lett 1990.
First major success of structure-based drug design. Saquinavir (1995) was the first HIV PR inhibitor approved; darunavir (2006) is the modern standard. The target remains under continuous evolutionary pressure — resistance mutations are a moving target.
Demonstrates: homodimer symmetry, allosteric flap dynamics, structure-based drug discovery, resistance evolution. Extremely well-characterised — thousands of PDB entries with inhibitors.