Substrate-driven chemotactic assembly in an enzyme cascade

Xi Zhao, Henri Palacci, Vinita Yadav, Michelle M. Spiering, Michael K. Gilson, Peter J. Butler, Henry Hess, Stephen J. Benkovic, Ayusman Sen

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Enzymatic catalysis is essential to cell survival. In many instances, enzymes that participate in reaction cascades have been shown to assemble into metabolons in response to the presence of the substrate for the first enzyme. However, what triggers metabolon formation has remained an open question. Through a combination of theory and experiments, we show that enzymes in a cascade can assemble via chemotaxis. We apply microfluidic and fluorescent spectroscopy techniques to study the coordinated movement of the first four enzymes of the glycolysis cascade: hexokinase, phosphoglucose isomerase, phosphofructokinase and aldolase. We show that each enzyme independently follows its own specific substrate gradient, which in turn is produced by the preceding enzymatic reaction. Furthermore, we find that the chemotactic assembly of enzymes occurs even under cytosolic crowding conditions.

Original languageEnglish (US)
Pages (from-to)311-317
Number of pages7
JournalNature Chemistry
Volume10
Issue number3
DOIs
StatePublished - Mar 1 2018

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Chemical Engineering(all)

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    Zhao, X., Palacci, H., Yadav, V., Spiering, M. M., Gilson, M. K., Butler, P. J., Hess, H., Benkovic, S. J., & Sen, A. (2018). Substrate-driven chemotactic assembly in an enzyme cascade. Nature Chemistry, 10(3), 311-317. https://doi.org/10.1038/NCHEM.2905