Document Detail


Differential reactivity of the functional sulfhydryl groups of cysteine-32 and cysteine-35 present in the reduced form of thioredoxin from Escherichia coli.
MedLine Citation:
PMID:  7000775     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Only one of the sulfhydryl groups from Cys-32 and Cys-35 in the active center of native Escherichia coli thioredoxin-(SH)2 was alkylated by excess iodoacetic acid at pH values below 8.0. Both groups reacted in the protein denatured with 4.5 M guanidine hydrochloride. The second order rate of alkylation of thioredoxin-(SH)2 with 1 eq of iodoacetic acid was pH-dependent and showed independent initial reactions of one thiolate ion with a pK value of 6.7 and a second with a pK value close to 9.0. The same pH dependence was observed for alkylation with iodoacetamide but the apparent rate constant, 107 M-1 S-1 at pH 7.2, was about 20-fold higher than the corresponding rate with iodoacetate. The sulfhydryl group with a pK value of 6.7 was shown to belong to Cys-32 by labeling thioredoxin with [14C]iodoacetic acid followed by complete alkylation with [3H]iodoacetate and amino acid sequence analysis of peptides from the active center. The abnormally low pK value of Cys-32 is suggested to arise by electrostatic influence from a positive charge on the amino group of Lys-36. A mechanism of action for thioredoxin-(SH)2 as a protein disulfide reductase has been formulated. This is based on an initial nucleophilic attack by the thiolate of Cys-32 with the formation of an unstable transient mixed disulfide involving Cys-32 and one of the sulfurs in the substrate. This is followed by a conformational change and a nucleophilic attack of Cys-35 to give the 14-membered disulfide ring in thioredoxin-S2 and the dithiol of the substrate.
Authors:
G B Kallis; A Holmgren
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  255     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1980 Nov 
Date Detail:
Created Date:  1981-01-29     Completed Date:  1981-01-29     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  10261-5     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Amino Acids / analysis
Bacterial Proteins / metabolism*
Binding Sites
Cysteine / analysis*
Dithionitrobenzoic Acid / pharmacology
Escherichia coli / metabolism*
Hydrogen-Ion Concentration
Iodoacetates
Kinetics
Protein Binding
Thioredoxin-Disulfide Reductase / metabolism
Thioredoxins / metabolism*
Chemical
Reg. No./Substance:
0/Amino Acids; 0/Bacterial Proteins; 0/Iodoacetates; 52-90-4/Cysteine; 52500-60-4/Thioredoxins; 69-78-3/Dithionitrobenzoic Acid; EC 1.8.1.9/Thioredoxin-Disulfide Reductase

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


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