Preprint Review Version 2 Preserved in Portico This version is not peer-reviewed

Structural Insights into Electrophiles and Electrophilic Metabolites Sensing and Signaling: The Missing Information

Version 1 : Received: 9 January 2023 / Approved: 12 January 2023 / Online: 12 January 2023 (04:08:43 CET)
Version 2 : Received: 19 February 2023 / Approved: 20 February 2023 / Online: 20 February 2023 (09:27:32 CET)

How to cite: Rogg, C.; Aye, Y. Structural Insights into Electrophiles and Electrophilic Metabolites Sensing and Signaling: The Missing Information. Preprints 2023, 2023010209. https://doi.org/10.20944/preprints202301.0209.v2. Rogg, C.; Aye, Y. Structural Insights into Electrophiles and Electrophilic Metabolites Sensing and Signaling: The Missing Information. Preprints 2023, 2023010209. https://doi.org/10.20944/preprints202301.0209.v2.

Abstract

Native reactive electrophile species (RES) are long-recognized regulators of pathophysiology; yet, knowledge surrounding how RES regulate context-specific biology remains limited. The latest technological advances in profiling and precision decoding of RES sensing and signaling have begun to bring about improved understanding of localized RES regulatory paradigms. However, studies in purified systems—prerequisites for gaining structure/function insights—prove challenging. We here introduce emerging chemical biology tools available to probe RES signaling, and the new knowledge that these tools have brought to the field. We next discuss existing structural data of RES-sensor proteins complexed with electrophilic metabolites or small molecule drugs (limited to < 300 Da), including challenges faced in acquiring homogenous RES-bound proteins. We further offer considerations that could promote enhanced understanding of RES regulation derived from three-dimensional structures of RES-modified proteins.

Keywords

electrophile signaling; reactive metabolites; crystal structures of protein-electrophile complexes

Subject

CHEMISTRY, Medicinal Chemistry

Comments (1)

Comment 1
Received: 20 February 2023
Commenter: Chloé Rogg
Commenter's Conflict of Interests: Author
Comment: We revised and expanded the manuscript to include suggestions made by reviewers.
+ Respond to this comment

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
Views 0
Downloads 0
Comments 1
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.