Adaptability and flexibility of HIV-1 protease

Authors


  • Enzyme: HIV-1 protease (EC: 3.4.23.16).

M. V. Hosur, Solid State Physics Division, Bhabha Atomic Research Centre, Mumbai, India-400085. Fax: +91 22 5515050, Tel.: +91 22 5593614, E-mail: hosur@magnum.barc.ernet.in

Abstract

Even though more than 200 three-dimensional structures of HIV-1 protease complexed to a variety of inhibitors are available in the Protein Data Bank; very few structures of unliganded protein have been determined. We have recently solved structures of unliganded HIV-1 protease tethered dimer mutants to resolutions of 1.9 Å and 2.1 Å, and have found that the flaps assume closed-flap conformation even in the absence of any bound ligand. We report comparison of the unliganded closed-flap structure with structures of HIV-1 protease inhibitor complexes with a view to accurately identifying structural changes that the ligand can induce on binding to HIV-1 protease in the crystal. These studies reveal that the least flexible region present in the active site of HIV-1 protease need not also be the least adaptable to external stress, thus highlighting the conceptual difference between flexibility and adaptability of proteins in general.

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