Discriminating changes in protein structure using tyrosine conjugation

Mahta Moinpour, Natalie K. Barker, Lindsay E. Guzman, John C. Jewett, Paul R. Langlais, Jacob C. Schwartz

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Chemical modification of proteins has been crucial in engineering protein-based therapies, targeted biopharmaceutics, molecular probes, and biomaterials. Here, we explore the use of a conjugation-based approach to sense alternative conformational states in proteins. Tyrosine has both hydrophobic and hydrophilic qualities, thus allowing it to be positioned at protein surfaces, or binding interfaces, or to be buried within a protein. Tyrosine can be conjugated with 4-phenyl-3H-1,2,4-triazole-3,5(4H)-dione (PTAD). We hypothesized that individual protein conformations could be distinguished by labeling tyrosine residues in the protein with PTAD. We conjugated tyrosine residues in a well-folded protein, bovine serum albumin (BSA), and quantified labeled tyrosine with liquid chromatography with tandem mass spectrometry. We applied this approach to alternative conformations of BSA produced in the presence of urea. The amount of PTAD labeling was found to relate to the depth of each tyrosine relative to the protein surface. This study demonstrates a new use of tyrosine conjugation using PTAD as an analytic tool able to distinguish the conformational states of a protein.

Original languageEnglish (US)
Pages (from-to)1784-1793
Number of pages10
JournalProtein Science
Issue number8
StatePublished - Aug 1 2020


  • conjugation
  • low complexity
  • protein folding
  • triazolinediones
  • tyrosine

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology


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