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

Piers Nash; Grant McFadden; Adrian Whitty

doi:10.1016/S0014-5793(00)01620-3

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

Piers Nash, Grant McFadden, Adrian Whitty

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

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. Copyright (C) 2000 Federation of European Biochemical Societies.

Original language	English (US)
Pages (from-to)	1-6
Number of pages	6
Journal	FEBS Letters
Volume	475
Issue number	1
DOIs	https://doi.org/10.1016/S0014-5793(00)01620-3
State	Published - Jun 9 2000
Externally published	Yes

Keywords

Inhibition kinetics
LFER
Poxvirus
Protease
Proteinaceous inhibitor
Structure-activity relationship

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

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10.1016/S0014-5793(00)01620-3

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title = "Application of linear free energy relationships to the serpin-proteinase inhibition mechanism",

abstract = "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. Copyright (C) 2000 Federation of European Biochemical Societies.",

keywords = "Inhibition kinetics, LFER, Poxvirus, Protease, Proteinaceous inhibitor, Structure-activity relationship",

author = "Piers Nash and Grant McFadden and Adrian Whitty",

note = "Funding Information: This work was supported by the Medical Research Council of Canada, National Cancer Institute (Canada) and Biogen, Inc. P.N. is a Medical Research Council (Canada) post-doctoral fellow, G.M. is a Medical Research Council of Canada Senior Scientist. We wish to thank Peter Gettins, Christopher Borysenko, and the late Stuart Stone for thought-provoking discussions.",

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T1 - Application of linear free energy relationships to the serpin-proteinase inhibition mechanism

AU - Nash, Piers

AU - McFadden, Grant

AU - Whitty, Adrian

N1 - Funding Information: This work was supported by the Medical Research Council of Canada, National Cancer Institute (Canada) and Biogen, Inc. P.N. is a Medical Research Council (Canada) post-doctoral fellow, G.M. is a Medical Research Council of Canada Senior Scientist. We wish to thank Peter Gettins, Christopher Borysenko, and the late Stuart Stone for thought-provoking discussions.

PY - 2000/6/9

Y1 - 2000/6/9

N2 - 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. Copyright (C) 2000 Federation of European Biochemical Societies.

AB - 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. Copyright (C) 2000 Federation of European Biochemical Societies.

KW - Inhibition kinetics

KW - LFER

KW - Poxvirus

KW - Protease

KW - Proteinaceous inhibitor

KW - Structure-activity relationship

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DO - 10.1016/S0014-5793(00)01620-3

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ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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