Version 1
: Received: 28 September 2019 / Approved: 30 September 2019 / Online: 30 September 2019 (07:53:42 CEST)
How to cite:
Long, M.J.C.; Wang, L.; Aye, Y. Getting the Right Grip? How Understanding Electrophile Selectivity Profiles Could Illuminate Our Understanding of Redox Signaling. Preprints2019, 2019090341 (doi: 10.20944/preprints201909.0341.v1).
Long, M.J.C.; Wang, L.; Aye, Y. Getting the Right Grip? How Understanding Electrophile Selectivity Profiles Could Illuminate Our Understanding of Redox Signaling. Preprints 2019, 2019090341 (doi: 10.20944/preprints201909.0341.v1).
Cite as:
Long, M.J.C.; Wang, L.; Aye, Y. Getting the Right Grip? How Understanding Electrophile Selectivity Profiles Could Illuminate Our Understanding of Redox Signaling. Preprints2019, 2019090341 (doi: 10.20944/preprints201909.0341.v1).
Long, M.J.C.; Wang, L.; Aye, Y. Getting the Right Grip? How Understanding Electrophile Selectivity Profiles Could Illuminate Our Understanding of Redox Signaling. Preprints 2019, 2019090341 (doi: 10.20944/preprints201909.0341.v1).
Abstract
Significance: Electrophile signaling is coming into focus as a bona fide cell signaling mechanism. The electrophilic regulation occurs typically through a sensing event (i.e., labeling of a protein) and a signaling event (the labeling event having an effect of the proteins activity, association, etc.). Recent advances: Herein, we focus on the first step of this process, electrophile sensing. Electrophile sensing is typically a deceptively simple reaction between the thiol of a protein-cysteine, of which there are around 200,000 in the human proteome, and a Michael acceptor, of which there are numerous flavors, including enals and enones. Recent data overall paint a picture that despite being a simple chemical reaction, electrophile sensing is a discerning process, showing labeling preferences that are often not in line with reactivity of the electrophile. Critical issues: With a view to trying to decide what brings about highly electrophile-reactive protein-cysteines, and how reactive these sensors may be, we discuss aspects of the thermodynamics and kinetics of covalent/non-covalent binding. Data made available by several laboratories indicate that it is likely that specific proteins exhibit highly stereo- and chemoselective electrophile sensing, which we take as good evidence for recognition between the electrophile and the protein prior to forming a covalent bond. Future directions: We propose experiments that could help us gain a better and more quantitative understanding of the mechanisms through which sensing comes about. We further extoll the importance of performing more detailed experiments on labeling and trying to standardize the way we assess protein-specific electrophile sensing.We propose experiments that could help us gain a better and more quantitative understanding of the mechanisms through which sensing comes about. We further extoll the importance of performing more detailed experiments on labeling and trying to standardize the way we assess protein-specific electrophile sensing.
Subject Areas
Covalent labeling; stereoselectivity; electrophile signaling; affinity; mechanism; kinetic control
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.
Marcus J. C. Long