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Multisite enzymes as a mechanism for bistability in reaction networks
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Hayes, Clarmyra, Feliu, Elisenda and Soyer, Orkun S. (2022) Multisite enzymes as a mechanism for bistability in reaction networks. ACS Synthetic Biology, 11 (2). pp. 596-607. doi:10.1021/acssynbio.1c00272 ISSN 2161-5063.
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WRAP-Multisite-enzymes-mechanism-bistability-reaction-networks-2022.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (1717Kb) | Preview |
Official URL: http://dx.doi.org/10.1021/acssynbio.1c00272
Abstract
Here, we focus on a common class of enzymes that have multiple substrate binding sites (multisite enzymes) and analyze their capacity to generate bistable dynamics in the reaction networks that they are embedded in. These networks include both substrate–product–substrate cycles and substrate-to-product conversion with subsequent product consumption. Using mathematical techniques, we show that the inherent binding and catalysis reactions arising from multiple substrate–enzyme complexes create a potential for bistable dynamics in such reaction networks. We construct a generic model of an enzyme with n-substrate binding sites and derive an analytical solution for the steady-state concentration of all enzyme–substrate complexes. By studying these expressions, we obtain a mechanistic understanding of bistability, derive parameter combinations that guarantee bistability, and show how changing specific enzyme kinetic parameters and enzyme levels can lead to bistability in reaction networks involving multisite enzymes. Thus, the presented findings provide a biochemical and mathematical basis for predicting and engineering bistability in multisite enzymes.
| Item Type: | Journal Article | |||||||||||||||
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| Subjects: | Q Science > QH Natural history Q Science > QP Physiology T Technology > TP Chemical technology |
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| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | |||||||||||||||
| Library of Congress Subject Headings (LCSH): | Synthetic biology , Enzyme kinetics, Protein engineering, Enzymes -- Stabilit, Cells -- Mathematical models | |||||||||||||||
| Journal or Publication Title: | ACS Synthetic Biology | |||||||||||||||
| Publisher: | American Chemical Society | |||||||||||||||
| ISSN: | 2161-5063 | |||||||||||||||
| Official Date: | 18 February 2022 | |||||||||||||||
| Dates: |
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| Volume: | 11 | |||||||||||||||
| Number: | 2 | |||||||||||||||
| Page Range: | pp. 596-607 | |||||||||||||||
| DOI: | 10.1021/acssynbio.1c00272 | |||||||||||||||
| Status: | Peer Reviewed | |||||||||||||||
| Publication Status: | Published | |||||||||||||||
| Access rights to Published version: | Open Access (Creative Commons) | |||||||||||||||
| Copyright Holders: | © 2022 The Authors. Published by American Chemical Society | |||||||||||||||
| Date of first compliant deposit: | 25 January 2022 | |||||||||||||||
| Date of first compliant Open Access: | 26 January 2022 | |||||||||||||||
| RIOXX Funder/Project Grant: |
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