Document Detail


Reversible Intramolecular Hydrogen Transfer between Protein Cysteine Thiyl Radicals and (alpha)C-H Bonds in Insulin: Control of Selectivity by Secondary Structure.
MedLine Citation:
PMID:  19053709     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The selective oxidative modification of proteins can have significant consequences for structure and function. Here, we show that protein cysteine thiyl radicals (CysS(*)) can reversibly abstract hydrogen atoms from the (alpha)C-H bonds of selected amino acids in a protein (insulin). CysS(*) were generated photolytically through homolysis of cystine and through photoionization of an aromatic residue, followed by one-electron reduction of cystine. Intramolecular hydrogen transfer was monitored through the covalent incorporation of deuterium into specific amino residues. Of 51 insulin amino residues, only six incorporated significant levels of deuterium: Leu(B6), Gly(B8), Ser(B9), Val(B18), Gly(B20), and Cys(A20). All these amino acids are located at the beginning/end or outside of alpha-helices and beta-sheets, in accordance with theory, which predicts that specifically the (alpha)C-H bonds of amino acids in these secondary structures have higher homolytic C-H bond dissociation energies compared to the (alpha)C-H bonds of amino acids in extended conformations. Through such hydrogen transfer mechanisms, thiyl radicals are able to catalyze the oxidation of amino acids in a protein through oxidants, which would not necessary directly react with these amino acids. This feature has important consequences for protein stability under conditions of oxidative stress and/or protein production in pharmaceutical biotechnology.
Authors:
Olivier Mozziconacci; Todd D Williams; Bruce A Kerwin; Christian Schöneich
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2008-11-17
Journal Detail:
Title:  The journal of physical chemistry. B     Volume:  -     ISSN:  1520-5207     ISO Abbreviation:  J Phys Chem B     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-12-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101157530     Medline TA:  J Phys Chem B     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Pharmaceutical Chemistry, 2095 Constant Avenue, University of Kansas, Lawrence, Kansas 66047; Mass Spectrometry Laboratory, University of Kansas, Lawrence, Kansas 66045; and the Department of Process and Product Development, Amgen Inc., Seattle, Washington 98119.
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