Skip Navigation


ToxSci Advance Access originally published online on October 16, 2008
Toxicological Sciences 2009 107(1):144-155; doi:10.1093/toxsci/kfn211
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
107/1/144    most recent
kfn211v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Li, B.
Right arrow Articles by Lockridge, O.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Li, B.
Right arrow Articles by Lockridge, O.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2008. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Tyrosines of Human and Mouse Transferrin Covalently Labeled by Organophosphorus Agents: A New Motif for Binding to Proteins that Have No Active Site Serine

Bin Li*, Lawrence M. Schopfer*, Hasmik Grigoryan*, Charles M. Thompson{dagger}, Steven H. Hinrichs{ddagger}, Patrick Masson§ and Oksana Lockridge*,1

* Eppley Institute, University of Nebraska Medical Center, Omaha, Nebraska 68198-6805 {dagger} Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, Montana 59812 {ddagger} Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska 68198 § Centre de Recherches d Service de Santé des Armées, Unité d'Enzymologie, BP87, 38702 La Tronche Cedex, France

1 To whom correspondence should be addressed at Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198-6805. Fax: (402) 559-4651. E-mail: olockrid{at}unmc.edu.

Received August 5, 2008; accepted September 26, 2008


  Abstract

The expectation from the literature is that organophosphorus (OP) agents bind to proteins that have an active site serine. However, transferrin, a protein with no active site serine, was covalently modified in vitro by 0.5mM 10-fluoroethoxyphosphinyl-N-biotinamido pentyldecanamide, chlorpyrifos oxon, diisopropylfluorophosphate, dichlorvos, sarin, and soman. The site of covalent attachment was identified by analyzing tryptic peptides in the mass spectrometer. Tyr 238 and Tyr 574 in human transferrin and Tyr 238, Tyr 319, Tyr 429, Tyr 491, and Tyr 518 in mouse transferrin were labeled by OP. Tyrosine in the small synthetic peptide ArgTyrThrArg made a covalent bond with diisopropylfluorophosphate, chlorpyrifos oxon, and dichlorvos at pH 8.3. These results, together with our previous demonstration that albumin and tubulin bind OP on tyrosine, lead to the conclusion that OP bind covalently to tyrosine, and that OP binding to tyrosine is a new OP-binding residue. The OP-reactive tyrosines are activated by interaction with Arg or Lys. It is suggested that many proteins in addition to those already identified may be modified by OP on tyrosine. The extent to which tyrosine modification by OP can occur in vivo and the toxicological implications of such modifications require further investigation.

Key Words: plasma; soman; sarin; mass spectrometry; tyrosine residue; transferrin.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.