dc.contributor.author | Mu, Weihua | |
dc.contributor.author | Kong, Jing | |
dc.contributor.author | Cao, Jianshu | |
dc.date.accessioned | 2022-07-22T15:22:27Z | |
dc.date.available | 2022-07-22T15:22:27Z | |
dc.date.issued | 2021 | |
dc.identifier.uri | https://hdl.handle.net/1721.1/143971 | |
dc.description.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. | en_US |
dc.language.iso | en | |
dc.publisher | American Chemical Society (ACS) | en_US |
dc.relation.isversionof | 10.1021/ACS.JPCLETT.1C00438 | en_US |
dc.rights | Creative Commons Attribution-Noncommercial-Share Alike | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | en_US |
dc.source | MIT web domain | en_US |
dc.title | Understanding the Optimal Cooperativity of Human Glucokinase: Kinetic Resonance in Nonequilibrium Conformational Fluctuations | en_US |
dc.type | Article | en_US |
dc.identifier.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). | |
dc.contributor.department | Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science | |
dc.contributor.department | Massachusetts Institute of Technology. Department of Chemistry | |
dc.relation.journal | Journal of Physical Chemistry Letters | en_US |
dc.eprint.version | Author's final manuscript | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dc.date.updated | 2022-07-22T15:19:08Z | |
dspace.orderedauthors | Mu, W; Kong, J; Cao, J | en_US |
dspace.date.submission | 2022-07-22T15:19:09Z | |
mit.journal.volume | 12 | en_US |
mit.journal.issue | 11 | en_US |
mit.license | OPEN_ACCESS_POLICY | |
mit.metadata.status | Authority Work and Publication Information Needed | en_US |