Academic Journal
ReDisulphID: A discovery platform for thiol redox sensors identifies a druggable site regulating p53 activation.
| Title: | ReDisulphID: A discovery platform for thiol redox sensors identifies a druggable site regulating p53 activation. |
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| Authors: | Coleman P; School of Cardiovascular and Metabolic Medicine & Sciences, King's College London, The British Heart Foundation Centre of Excellence, The Rayne Institute, St Thomas' Hospital, London, SE1 7EH, UK. Electronic address: pierre.coleman@kcl.ac.uk., Laddach A; Nervous System Development and Homeostasis Laboratory, the Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK., Anderson R; School of Cardiovascular and Metabolic Medicine & Sciences, King's College London, The British Heart Foundation Centre of Excellence, The Rayne Institute, St Thomas' Hospital, London, SE1 7EH, UK., Yang X; Proteomics Facility, Centre of Excellence for Mass Spectrometry, King's College London, The James Black Centre, Denmark Hill Campus, London, SE5 9NU, UK., Kumar R; School of Cardiovascular and Metabolic Medicine & Sciences, King's College London, The British Heart Foundation Centre of Excellence, James Black Centre, 125 Coldharbour Lane, London, SE5 9NU, UK., Shah A; School of Cardiovascular and Metabolic Medicine & Sciences, King's College London, The British Heart Foundation Centre of Excellence, James Black Centre, 125 Coldharbour Lane, London, SE5 9NU, UK., Fraternali F; Institute of Structural and Molecular Biology, University College London, London, WC1E 6BT, UK; Research Department of Structural and Molecular Biology, Division of Biosciences, University College London, London, WC1E 6BT, UK; Department of Biological Sciences, Birkbeck, University of London, London, WC1E 7HX, UK., Burgoyne JR; School of Cardiovascular and Metabolic Medicine & Sciences, King's College London, The British Heart Foundation Centre of Excellence, The Rayne Institute, St Thomas' Hospital, London, SE1 7EH, UK. Electronic address: joseph.r.burgoyne@kcl.ac.uk. |
| Source: | Redox biology [Redox Biol] 2026 Jul; Vol. 94, pp. 104196. Date of Electronic Publication: 2026 Apr 29. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Elsevier, B.V Country of Publication: Netherlands NLM ID: 101605639 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2213-2317 (Electronic) Linking ISSN: 22132317 NLM ISO Abbreviation: Redox Biol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [Amsterdam]: Elsevier, B.V., [2013]- |
| MeSH Terms: | Tumor Suppressor Protein p53*/metabolism , Tumor Suppressor Protein p53*/chemistry , Tumor Suppressor Protein p53*/genetics , Sulfhydryl Compounds*/metabolism , Sulfhydryl Compounds*/chemistry , Disulfides*/chemistry , Disulfides*/metabolism, Computational Biology/methods ; Oxidation-Reduction ; Humans ; Signal Transduction ; Drug Discovery |
| Abstract: | Thiol redox sensors in proteins are emerging as key therapeutic targets, as they govern fundamental signalling pathways and provide crucial sites for covalent drug development. A key mediator of their function is the presence of redox-active disulphides, which act as molecular switches due to their ability to induce reversible protein conformational changes. However, despite their importance in cellular regulation and therapeutic relevance, only a limited number of redox-active disulphides have been identified to date. To address this, we developed ReDisulphID, a structural bioinformatics platform that systematically identifies druggable redox-active disulphides. Using this platform, we discovered novel druggable redox sensors in MLYCD, TFIIB, and PEPD. Functional analysis of PEPD revealed that its redox sensor activates the tumour suppressor p53. Furthermore, we identified a compound that activates p53 through direct thiol modification of the sensor in PEPD, demonstrating how ReDisulphID can advance the discovery of protein redox sensors and support thiol-targeted drug development. (Copyright © 2026 The Authors. Published by Elsevier B.V. All rights reserved.) |
| Competing Interests: | Declaration of competing interest We confirm the authors have no conflict of interest to declare. |
| Contributed Indexing: | Keywords: Disulphide; PEPD; Redox sensor; Thiol; p53 |
| Substance Nomenclature: | 0 (Tumor Suppressor Protein p53) 0 (Sulfhydryl Compounds) 0 (Disulfides) |
| Entry Date(s): | Date Created: 20260507 Date Completed: 20260613 Latest Revision: 20260613 |
| Update Code: | 20260613 |
| PubMed Central ID: | PMC13157088 |
| DOI: | 10.1016/j.redox.2026.104196 |
| PMID: | 42097034 |
| Database: | MEDLINE |
| ISSN: | 2213-2317 |
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| DOI: | 10.1016/j.redox.2026.104196 |