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Correlating Conformational Shift Induction with Altered Inhibitor Potency in a Multidrug Resistant HIV-1 Protease Variant

Year: 2012

Type: article

Abstract: Inhibitor-induced conformational ensemble shifts in a multidrug resistant HIV-1 protease variant, MDR769, are characterized by site-directed spin labeling double electron-electron resonance spectroscopy. For MDR769 compared to the native enzyme, changes in inhibitor IC(50) values are related to a parameter defined as |ΔC|, which is the relative change in the inhibitor-induced shift to the closed state. Specifically, a linear correlation is found between |ΔC| and the magnitude of the change in IC(50), provided that inhibitor binding is not too weak. Moreover, inhibitors that exhibit MDR769 resistance no longer induce a strong shift to a closed conformational ensemble as seen previously in the native enzyme.

Source: Biochemistry

DOI: 10.1021/bi301010z

Authors: Ian Mitchelle S. de Vera, Mandy E. Blackburn, Gail E. Fanucci

Institutions: University of Florida, University of Massachusetts Amherst

Language: English

Topic: Electron Spin Resonance Studies

Subfield: Biophysics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funder: National Center for Research Resources