A Chemical Probe for Dehydrobutyrine
Abstract
Bacterial phosphothreonine lyases, or phospholyases, catalyze a unique post‐translational modification that introduces dehydrobutyrine (Dhb) or dehydroalanine (Dha) in place of phosphothreonine or phosphoserine residues, respectively. We report the use of a phospha‐Michael reaction to label proteins and peptides modified with Dha or Dhb. We demonstrate that a nucleophilic phosphine probe is able to modify Dhb‐containing proteins and peptides that were recalcitrant to reaction with thiol or amine nucleophiles under mild aqueous conditions. Furthermore, we used this reaction to detect multiple Dhb‐modified proteins in mammalian cell lysates, including histone H3, a previously unknown target of phospholyases. This method should prove useful for identifying new phospholyase targets, profiling the biomarkers of bacterial infection, and developing enzyme‐mediated strategies for bioorthogonal labeling in living cells.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 06, 2020
- Source ID
- 10.1002/ange.202003631
Entities
People
- Caitlin J Hill
- Imran H Khan
- Kaitlin A Chambers
- Nile S Abularrage
- Rebecca A Scheck
Organizations
- Arnold and Mabel Beckman Foundation
- Intelligence Advanced Research Projects Activity
- Massachusetts Institute of Technology
- Tufts University