1. HIV-1 Protease HIV-1 Protease is one of the targets in the therapeutic treatment of AIDS. It cleaves the nascent polyproteins of HIV-1 and plays an essential role in viral replication. There are quite a few different inhibitors in existence for HIV-1 Protease. Due to the rapid rate of viral replication and the high error rate of reverse transcriptase result in HIV-1 mutants resistant to inhibitor action. Peptide bond hydrolysis

2. Collectively, a total of 16 hydrogen bonds were identified in the interaction between HIV-1 protease and KNI-272. 9 of the 16 hydrogen bonding interactions were water mediated.

3. HIV-1 Protease enzyme molecule is a homodimer of two polypeptide chains each containing 99 amino acid residues, and a single active site formed at the dimer interface. The two monomers are covalently joined through a short linker.

4. Protein structure with MVT-101 inhibitor (shown in green)

5. Vertical view

7. Tiger Face!

9. Interactions betwixt HIV-1 protease and its inhibitor should strongly depend on the ionization state of the catalytic active site; KNI- 272 affinity to HIV-1 protease depends on pH. At maximum affinity, only Asp-25 is protonated. Below is the KNI-272 inhibitor bonded to the active site of HIV-1 Protease. The main interactions in the active site involve hydrogen bonding with four aspartates. Asp-25 is in red, while Asp-29, Asp 125, and Asp 129 are green. Also shown are three water molecules, HOH-301, HOH566, HOH608, which play a crucial role in bonding.

11. AD78 KB62

12. KB60 Darunavir

13. two Asp-Thr-Gly catalytic triads (residue numbers 25, 26, and 27 on one chain and 125, 126, and 127 on the second). The two Asp's act as the main catalytic residues in the active site and use a water molecule to help break the protein chain that binds in the tunnel.

15. HIV-1 Protease Inhibitor Km (μM)Vmax (nmol/(min*mg) Saquinavir1.430.7 Nelfinavir3.620.8 Indinavir2.199.9 Amprenavir46.996.4 Ritonavir0.0677.3 Saquinavir1.1993.6 Indinavir0.47112.2