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Discriminating between Concerted and Sequential Allosteric Mechanisms by Comparing Equilibrium and Kinetic Hill Coefficients

[Image: see text] Hill coefficients, which provide a measure of cooperativity in ligand binding, can be determined for equilibrium (or steady-state) data by measuring fractional saturation (or initial reaction velocities) as a function of ligand concentration. Hill coefficients can also be determine...

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Autores principales: Horovitz, Amnon, Mondal, Tridib
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2021
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884004/
https://www.ncbi.nlm.nih.gov/pubmed/33397110
http://dx.doi.org/10.1021/acs.jpcb.0c09351
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author Horovitz, Amnon
Mondal, Tridib
author_facet Horovitz, Amnon
Mondal, Tridib
author_sort Horovitz, Amnon
collection PubMed
description [Image: see text] Hill coefficients, which provide a measure of cooperativity in ligand binding, can be determined for equilibrium (or steady-state) data by measuring fractional saturation (or initial reaction velocities) as a function of ligand concentration. Hill coefficients can also be determined for transient kinetic data from plots of the observed rate constant of the ligand-promoted conformational change as a function of ligand concentration. Here, it is shown that the ratio of the values of these two Hill coefficients can provide insight into the allosteric mechanism. Cases when the value of the kinetic Hill coefficient is equal to or greater than the value of the equilibrium coefficient indicate concerted transitions whereas ratios smaller than one indicate a sequential transition. The derivations in this work are for symmetric dimers but are expected to have general applicability for homo-oligomers.
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spelling pubmed-78840042021-02-16 Discriminating between Concerted and Sequential Allosteric Mechanisms by Comparing Equilibrium and Kinetic Hill Coefficients Horovitz, Amnon Mondal, Tridib J Phys Chem B [Image: see text] Hill coefficients, which provide a measure of cooperativity in ligand binding, can be determined for equilibrium (or steady-state) data by measuring fractional saturation (or initial reaction velocities) as a function of ligand concentration. Hill coefficients can also be determined for transient kinetic data from plots of the observed rate constant of the ligand-promoted conformational change as a function of ligand concentration. Here, it is shown that the ratio of the values of these two Hill coefficients can provide insight into the allosteric mechanism. Cases when the value of the kinetic Hill coefficient is equal to or greater than the value of the equilibrium coefficient indicate concerted transitions whereas ratios smaller than one indicate a sequential transition. The derivations in this work are for symmetric dimers but are expected to have general applicability for homo-oligomers. American Chemical Society 2021-01-05 2021-01-14 /pmc/articles/PMC7884004/ /pubmed/33397110 http://dx.doi.org/10.1021/acs.jpcb.0c09351 Text en © 2021 American Chemical Society This is an open access article published under a Creative Commons Attribution (CC-BY) License (http://pubs.acs.org/page/policy/authorchoice_ccby_termsofuse.html) , which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
spellingShingle Horovitz, Amnon
Mondal, Tridib
Discriminating between Concerted and Sequential Allosteric Mechanisms by Comparing Equilibrium and Kinetic Hill Coefficients
title Discriminating between Concerted and Sequential Allosteric Mechanisms by Comparing Equilibrium and Kinetic Hill Coefficients
title_full Discriminating between Concerted and Sequential Allosteric Mechanisms by Comparing Equilibrium and Kinetic Hill Coefficients
title_fullStr Discriminating between Concerted and Sequential Allosteric Mechanisms by Comparing Equilibrium and Kinetic Hill Coefficients
title_full_unstemmed Discriminating between Concerted and Sequential Allosteric Mechanisms by Comparing Equilibrium and Kinetic Hill Coefficients
title_short Discriminating between Concerted and Sequential Allosteric Mechanisms by Comparing Equilibrium and Kinetic Hill Coefficients
title_sort discriminating between concerted and sequential allosteric mechanisms by comparing equilibrium and kinetic hill coefficients
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884004/
https://www.ncbi.nlm.nih.gov/pubmed/33397110
http://dx.doi.org/10.1021/acs.jpcb.0c09351
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