Optimizing enzymatic catalysts for rapid turnover of substrates with low enzyme sequestration
File(s)1905.00555v2.pdf (2.03 MB)
Accepted version
Author(s)
Deshpande, A
Ouldridge, T
Type
Journal Article
Abstract
Enzymes are central to both metabolism and information processing in cells. In both cases, an enzyme’s ability to accelerate a reaction without being consumed in the reaction is crucial. Nevertheless, enzymes are transiently sequestered when they bind to their substrates; this sequestration limits activity and potentially compromises information processing and signal transduction. In this article, we analyse the mechanism of enzyme–substrate catalysis from the perspective of minimizing the load on the enzymes through sequestration, while maintaining at least a minimum reaction flux. In particular, we ask: which binding free energies of the enzyme–substrate and enzyme–product reaction intermediates minimize the fraction of enzymes sequestered in complexes, while sustaining a certain minimal flux? Under reasonable biophysical assumptions, we find that the optimal design will saturate the bound on the minimal flux and reflects a basic trade-off in catalytic operation. If both binding free energies are too high, there is low sequestration, but the effective progress of the reaction is hampered. If both binding free energies are too low, there is high sequestration, and the reaction flux may also be suppressed in extreme cases. The optimal binding free energies are therefore neither too high nor too low, but in fact moderate. Moreover, the optimal difference in substrate and product binding free energies, which contributes to the thermodynamic driving force of the reaction, is in general strongly constrained by the intrinsic free-energy difference between products and reactants. Both the strategies of using a negative binding free-energy difference to drive the catalyst-bound reaction forward and of using a positive binding free-energy difference to enhance detachment of the product are limited in their efficacy.
Date Issued
2020-12-01
Online Publication Date
2021-10-12T23:01:55Z
Date Acceptance
2020-09-11
ISSN
0340-1200
Publisher
Springer
Start Page
653
End Page
668
Journal / Book Title
Biological Cybernetics: communication and control in organisms and automata
Volume
114
Copyright Statement
© Springer-Verlag GmbH Germany, part of Springer Nature 2020. The final publication is available at Springer via https://link.springer.com/article/10.1007/s00422-020-00846-6
Sponsor
The Royal Society
Grant Number
UF150067
Subjects
Science & Technology
Technology
Life Sciences & Biomedicine
Computer Science, Cybernetics
Neurosciences
Computer Science
Neurosciences & Neurology
THEORETICAL DESCRIPTION
COMPUTATIONAL DESIGN
MOLECULAR-SYSTEMS
STEADY-STATE
THERMODYNAMICS
ULTRASENSITIVITY
KINETICS
FORCE
q-bio.MN
q-bio.MN
Neurology & Neurosurgery
0299 Other Physical Sciences
0801 Artificial Intelligence and Image Processing
1702 Cognitive Sciences
Publication Status
Published
Date Publish Online
2020-10-12