Download MendeleyCrystallographic study of multi-drug resistant HIV-1 protease lopinavir complex: mechanism of drug recognition and resistance.
Liu, Z., Yedidi, R.S., Wang, Y., Dewdney, T.G., Reiter, S.J., Brunzelle, J.S., Kovari, I.A., Kovari, L.C.(2013) Biochem Biophys Res Commun 437: 199-204
- PubMed: 23792096
- DOI: https://doi.org/10.1016/j.bbrc.2013.06.027
- Primary Citation of Related Structures:
4L1A - PubMed Abstract:
Lopinavir (LPV) is a second generation HIV-1 protease inhibitor. Drug resistance has rapidly emerged against LPV since its US FDA approval on September 15, 2000. Mutations at residues 32I, L33F, 46I, 47A, I54V, V82A, I84V, and L90M render the protease drug resistant against LPV. We report the crystal structure of a clinical isolate multi-drug resistant (MDR) 769 HIV-1 protease (resistant mutations at residues 10, 36, 46, 54, 62, 63, 71, 82, 84, and 90) complexed with LPV and the in vitro enzymatic IC50 of LPV against MDR 769. The structural and functional studies demonstrate significant drug resistance of MDR 769 against LPV, arising from reduced interactions between LPV and the protease target.
Organizational Affiliation:
Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, Detroit, MI 48201, United States.
