Real time NMR monitoring of local unfolding of HIV‐1 protease tethered dimer driven by autolysis

FEBS Letters

Panchal, Sanjay C.¹  Bhavesh, Neel S.¹  Hosur, R.V.¹ 

[1] Department of Chemical Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Mumbai 400 005, India

关键词: Human immunodeficiency virus-1 protease;    Autolysis;    Local unfolding;    Real time nuclear magnetic resonance;    HIV;    human immunodeficiency virus;    HSQC;    heteronuclear single quantum coherence;    NMR;    nuclear magnetic resonance;    PAGE;    polyacrylamide gel electrophoresis;    SDS;    sodium dodecyl sulphate;   

DOI  :  10.1016/S0014-5793(01)02426-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Structural studies in proteases have been hampered because of their inherent autolytic function. However, since autolysis is known to be mediated via protein unfolding, careful monitoring of the autolytic reaction has the potential to throw light on the folding–unfolding equilibria. In this paper we describe real time nuclear magnetic resonance investigations on the tethered dimer construct of the human immunodeficiency virus-1 protease, which have yielded insights into the relative stabilities of several residues in the protein. The residues lying along the active site (bottom, side and top of the active site) and those in helix have lower unfolding free energy values than the other parts of the protein. The residue level stability differences suggest that the protein is well suited to adjust itself in almost all the regions of its structure, as and when perturbations occur, either due to ligand binding or due to mutations.

【 授权许可】

Unknown