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. Preprints2023, 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.
Cite as:
Rogg, C.; Aye, Y. Structural Insights into Electrophiles and Electrophilic Metabolites Sensing and Signaling: The Missing Information. Preprints2023, 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
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Commenter: Chloé Rogg
Commenter's Conflict of Interests: Author