Understanding the Optimal Cooperativity of Human Glucokinase: Kinetic Resonance in Nonequilibrium Conformational Fluctuations
Name
JPCLMu_2021.pdf
Description
Accepted version
Size
735.35 KB
Format
Adobe PDF
Checksum (MD5)
be7b548123591e980342397774d4127e
Author(s)
Mu, Weihua
Kong, Jing
Cao, Jianshu
Date Issued
2021
Journal
Journal of Physical Chemistry Letters
Publisher
American Chemical Society (ACS)
Citation
Mu, Weihua, Kong, Jing and Cao, Jianshu. 2021. "Understanding the Optimal Cooperativity of Human Glucokinase: Kinetic Resonance in Nonequilibrium Conformational Fluctuations." Journal of Physical Chemistry Letters, 12 (11).
Version
Author's final manuscript
Abstract
The cooperativity of a monomeric enzyme arises from dynamic correlation instead of spatial correlation and is a consequence of nonequilibrium conformation fluctuations. We investigate the conformation-modulated kinetics of human glucokinase, a monomeric enzyme with important physiological functions, using a five-state kinetic model. We derive the non-Michealis-Menten (MM) correction term of the activity (i.e., turnover rate), predict its relationship to cooperativity, and reveal the violation of conformational detailed balance. Most importantly, we reproduce and explain the observed resonance effect in human glucokinase (i.e., maximal cooperativity when the conformational fluctuation rate is comparable to the catalytic rate). With the realistic parameters, our theoretical results are in quantitative agreement with the reported measurement by Miller and co-workers. The analysis can be extended to a general chemical network beyond the five-state model, suggesting the generality of kinetic cooperativity and resonance.
MIT Department
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Massachusetts Institute of Technology. Department of Chemistry
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1021/ACS.JPCLETT.1C00438
