3O9C

Crystal Structure of wild-type HIV-1 Protease in complex with kd20

Summary for 3O9C

• Entry DOI: 10.2210/pdb3o9c/pdb
• Related: 3O99 3O9A 3O9B 3O9D 3O9E 3O9F 3O9G 3O9H 3O9I
• Descriptor: Pol polyprotein, (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl [(1S,2R)-3-{(1,3-benzodioxol-5-ylsulfonyl)[(2S)-2-methylbutyl]amino}-1-benzyl-2-hydroxypropyl]carbamate (3 entities in total)
• Functional Keywords: hiv-1 protease, drug resistance, drug design, protease inhibitors, aids, aspartyl protease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Human immunodeficiency virus 1 (HIV-1)
• Total number of polymer chains: 2
• Total formula weight: 22222.27

Authors

Schiffer, C.A.,Nalam, M.N.L. (deposition date: 2010-08-04, release date: 2011-08-10, Last modification date: 2024-04-03)

Primary citation

Nalam, M.N.,Ali, A.,Reddy, G.S.,Cao, H.,Anjum, S.G.,Altman, M.D.,Yilmaz, N.K.,Tidor, B.,Rana, T.M.,Schiffer, C.A.
Substrate envelope-designed potent HIV-1 protease inhibitors to avoid drug resistance.
Chem.Biol., 20:1116-1124, 2013

PubMed Abstract: The rapid evolution of HIV under selective drug pressure has led to multidrug resistant (MDR) strains that evade standard therapies. We designed highly potent HIV-1 protease inhibitors (PIs) using the substrate envelope model, which confines inhibitors within the consensus volume of natural substrates, providing inhibitors less susceptible to resistance because a mutation affecting such inhibitors will simultaneously affect viral substrate processing. The designed PIs share a common chemical scaffold but utilize various moieties that optimally fill the substrate envelope, as confirmed by crystal structures. The designed PIs retain robust binding to MDR protease variants and display exceptional antiviral potencies against different clades of HIV as well as a panel of 12 drug-resistant viral strains. The substrate envelope model proves to be a powerful strategy to develop potent and robust inhibitors that avoid drug resistance.

PubMed: 24012370
DOI: 10.1016/j.chembiol.2013.07.014

Experimental method

X-RAY DIFFRACTION (1.85 Å)