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Full-Text Articles in Biochemistry, Biophysics, and Structural Biology
Structural And Thermodynamic Basis Of Amprenavir/Darunavir And Atazanavir Resistance In Hiv-1 Protease With Mutations At Residue 50, Seema Mittal, Rajintha Bandaranayake, Nancy King, Moses Prabu-Jeyabalan, Madhavi Nalam, Ellen Nalivaika, Nese Yilmaz, Celia Schiffer
Structural And Thermodynamic Basis Of Amprenavir/Darunavir And Atazanavir Resistance In Hiv-1 Protease With Mutations At Residue 50, Seema Mittal, Rajintha Bandaranayake, Nancy King, Moses Prabu-Jeyabalan, Madhavi Nalam, Ellen Nalivaika, Nese Yilmaz, Celia Schiffer
Celia A. Schiffer
Drug resistance occurs through a series of subtle changes that maintain substrate recognition but no longer permit inhibitor binding. In HIV-1 protease, mutations at I50 are associated with such subtle changes that confer differential resistance to specific inhibitors. Residue I50 is located at the protease flap tips, closing the active site upon ligand binding. Under selective drug pressure, I50V/L substitutions emerge in patients, compromising drug susceptibility and leading to treatment failure. The I50V substitution is often associated with amprenavir (APV) and darunavir (DRV) resistance, while the I50L substitution is observed in patients failing atazanavir (ATV) therapy. To explain how APV, …
Molecular Basis For Drug Resistance In Hiv-1 Protease, Akbar Ali, Rajintha M. Bandaranayake, Yufeng Cai, Nancy M. King, Madhavi Kolli, Seema Mittal, Jennifer E. Foulkes-Murzycki, Madhavi N. L. Nalam, Ellen A. Nalivaika, Aysegul Ozen, Moses Prabu-Jeyabalan, Kelly Thayer, Celia A. Schiffer
Molecular Basis For Drug Resistance In Hiv-1 Protease, Akbar Ali, Rajintha M. Bandaranayake, Yufeng Cai, Nancy M. King, Madhavi Kolli, Seema Mittal, Jennifer E. Foulkes-Murzycki, Madhavi N. L. Nalam, Ellen A. Nalivaika, Aysegul Ozen, Moses Prabu-Jeyabalan, Kelly Thayer, Celia A. Schiffer
Celia A. Schiffer
HIV-1 protease is one of the major antiviral targets in the treatment of patients infected with HIV-1. The nine FDA approved HIV-1 protease inhibitors were developed with extensive use of structure-based drug design, thus the atomic details of how the inhibitors bind are well characterized. From this structural understanding the molecular basis for drug resistance in HIV-1 protease can be elucidated. Selected mutations in response to therapy and diversity between clades in HIV-1 protease have altered the shape of the active site, potentially altered the dynamics and even altered the sequence of the cleavage sites in the Gag polyprotein. All …