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    
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.
Olivier Mozziconacci; Todd D Williams; Bruce A Kerwin; Christian Schöneich
Related Documents :
6849309 - Decreased incorporation of 14c-glucosamine relative to 3h-n-acetyl glucosamine in the i...
25321659 - The effect of omega-3 fatty acids on bronchial hyperresponsiveness, sputum eosinophilia...
168949 - Nutritional control of differentiation (sclerotization) of the myxomycete physarum flav...
24270219 - Guanidine bridged nucleic acid (guna): an effect of a cationic bridged nucleic acid on ...
18087869 - Chemical profile and amino acids composition of edible mushrooms pleurotus sajor-caju.
23648399 - Human studies using isotope labeled fatty acids: answered and unanswered questions.
14758039 - Comparative pharmacokinetic behavior of glycyrrhetic acid after oral administration of ...
11760999 - Unusually high levels of non-saponifiable lipids in the fishes escolar and rudderfish i...
9873579 - Two novel oleanolic acid saponins having a sialyl lewis x mimetic structure from achyra...
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:  -    
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.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Synthesis of SAPO-34 crystals in the presence of crystal growth inhibitors.
Next Document:  Physical Properties of Oriented Thin Films Formed by the Electrostatic Complexation of Sulfonated Po...