Turning up the heat mimics allosteric signaling in imidazole-glycerol phosphate synthase

Federica Maschietto (), Uriel N. Morzan (), Florentina Tofoleanu, Aria Gheeraert, Apala Chaudhuri, Gregory W. Kyro, Peter Nekrasov, Bernard Brooks, J. Patrick Loria (), Ivan Rivalta () and Victor S. Batista ()
Additional contact information
Federica Maschietto: Yale University
Uriel N. Morzan: International Center for Theoretical Physics
Florentina Tofoleanu: Yale University
Aria Gheeraert: ENSL, CNRS, Laboratoire de Chimie UMR 5182
Apala Chaudhuri: Yale University
Gregory W. Kyro: Yale University
Peter Nekrasov: Yale University
Bernard Brooks: National Institutes of Health
J. Patrick Loria: Yale University
Ivan Rivalta: ENSL, CNRS, Laboratoire de Chimie UMR 5182
Victor S. Batista: Yale University

Nature Communications, 2023, vol. 14, issue 1, 1-13

Abstract: Abstract Allosteric drugs have the potential to revolutionize biomedicine due to their enhanced selectivity and protection against overdosage. However, we need to better understand allosteric mechanisms in order to fully harness their potential in drug discovery. In this study, molecular dynamics simulations and nuclear magnetic resonance spectroscopy are used to investigate how increases in temperature affect allostery in imidazole glycerol phosphate synthase. Results demonstrate that temperature increase triggers a cascade of local amino acid-to-amino acid dynamics that remarkably resembles the allosteric activation that takes place upon effector binding. The differences in the allosteric response elicited by temperature increase as opposed to effector binding are conditional to the alterations of collective motions induced by either mode of activation. This work provides an atomistic picture of temperature-dependent allostery, which could be harnessed to more precisely control enzyme function.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-023-37956-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37956-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-37956-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().