Application of linear free energy relationships to the serpin–proteinase inhibition mechanism

FEBS Letters

Nash, Piers³  McFadden, Grant²  Whitty, Adrian¹ 

[1] Protein Engineering Department, BIOGEN Inc., 14 Cambridge Center, Cambridge, MA 02142, USA;John P. Robarts Research Institute and Department of Microbiology and Immunology, University of Western Ontario, London, Ont., Canada N6G 2V4;Department of Biochemistry, University of Alberta, Edmonton, Alta., Canada T6G 2H7

关键词: Inhibition kinetics;    LFER;    Protease;    Proteinaceous inhibitor;    Poxvirus;    Structure–activity relationship;   

DOI  :  10.1016/S0014-5793(00)01620-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Linear free energy relationships can be used to link the changes in rate constant for a reaction to changes in the equilibrium caused by alterations in structure. While they have most often been used in the analysis of chemical reactions, they have also been employed to resolve questions in enzymology and protein folding. Here we analyze the reaction of a serpin with a panel of six serine proteinases, and observe that a linear free energy relationship exists between the true second-order rate constant for reaction, k _inh, and the inhibition constant, K _I, indicating that formation of the covalent serpin–enzyme complex may be reversible.

【 授权许可】

Unknown