Molecular basis for the allosteric activation mechanism of the heterodimeric imidazole glycerol phosphate synthase complex

23Citations
Citations of this article
28Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Imidazole glycerol phosphate synthase (HisFH) is a heterodimeric bienzyme complex operating at a central branch point of metabolism. HisFH is responsible for the HisH-catalyzed hydrolysis of glutamine to glutamate and ammonia, which is then used for a cyclase reaction by HisF. The HisFH complex is allosterically regulated but the underlying mechanism is not well understood. Here, we elucidate the molecular basis of the long range, allosteric activation of HisFH. We establish that the catalytically active HisFH conformation is only formed when the substrates of both HisH and HisF are bound. We show that in this conformation an oxyanion hole in the HisH active site is established, which rationalizes the observed 4500-fold allosteric activation compared to the inactive conformation. In solution, the inactive and active conformations are in a dynamic equilibrium and the HisFH turnover rates correlate with the population of the active conformation, which is in accordance with the ensemble model of allostery.

Cite

CITATION STYLE

APA

Wurm, J. P., Sung, S., Kneuttinger, A. C., Hupfeld, E., Sterner, R., Wilmanns, M., & Sprangers, R. (2021). Molecular basis for the allosteric activation mechanism of the heterodimeric imidazole glycerol phosphate synthase complex. Nature Communications, 12(1). https://doi.org/10.1038/s41467-021-22968-6

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free