Journal article
Formaldehyde reacts with N-terminal proline residues to give bicyclic aminals
- Abstract:
-
Formaldehyde (HCHO) is a potent electrophile that is toxic above threshold levels, but which is also produced in the nuclei of eukaryotic cells by demethylases. We report studies with the four canonical human histones revealing that histone H2B reacts with HCHO, including as generated by a histone demethylase, to give a stable product. NMR studies show that HCHO reacts with the N-terminal proline and associated amide of H2B to give a 5,5-bicyclic aminal that is relatively stable to competition with HCHO scavengers. While the roles of histone modification by this reaction require further investigation, we demonstrated the potential of N-terminal aminal formation to modulate protein function by conducting biochemical and cellular studies on the effects of HCHO on catalysis by 4-oxalocrotonate tautomerase, which employs a nucleophilic N-terminal proline. The results suggest that reactions of N-terminal residues with HCHO and other aldehydes have potential to alter protein function.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
Actions
Access Document
- Files:
-
-
(Preview, Version of record, pdf, 1.8MB, Terms of use)
-
- Publisher copy:
- 10.1038/s42004-022-00801-5
Authors
- Publisher:
- Springer Nature
- Journal:
- Communications Chemistry More from this journal
- Volume:
- 6
- Issue:
- 1
- Article number:
- 12
- Publication date:
- 2023-01-13
- Acceptance date:
- 2022-12-20
- DOI:
- EISSN:
-
2399-3669
- Pmid:
-
36698022
- Language:
-
English
- Keywords:
- Pubs id:
-
1324890
- Local pid:
-
pubs:1324890
- Deposit date:
-
2023-03-16
- ARK identifier:
Terms of use
- Copyright holder:
- John et al.
- Copyright date:
- 2023
- Rights statement:
- © The Author(s) 2023. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
- Licence:
- CC Attribution (CC BY)
If you are the owner of this record, you can report an update to it here: Report update to this record