Reactivity of Thioredoxin as a Protein Thiol-Disulfide Oxidoreductase

被引：116

作者：

Cheng, Zhiyong ^{[1
]}

Zhang, Jinfeng ^{[2
]}

Ballou, David P. ^{[1
]}

Williams, Charles H., Jr. ^{[1
]}

机构：

[1] Univ Michigan, Sch Med, Dept Biol Chem, Ann Arbor, MI 48109 USA

[2] Florida State Univ, Dept Stat, Tallahassee, FL 32306 USA

来源：

CHEMICAL REVIEWS | 2011年 / 111卷 / 09期

关键词：

ESCHERICHIA-COLI THIOREDOXIN; ACTIVE-SITE CYSTEINE; PARASITE PLASMODIUM-FALCIPARUM; OXIDATION-REDUCTION PROPERTIES; MOLECULE FORCE SPECTROSCOPY; STAPHYLOCOCCUS-AUREUS DSBA; ASPARTIC-ACID; 26; REDOX PROPERTIES; CHLOROPLAST FRUCTOSE-1,6-BISPHOSPHATASE; CRYSTAL-STRUCTURE;

D O I：

10.1021/cr100006x

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The reactivity of thioredoxin as a protein thiol-disulfide oxidoreductase is examined. The deprotonation of the redox active thiols in the CXXC motif is critical for the generation of the nucleophilic thiolate form that will attack the target disulfide in thiol-disulfide interchange reactions. The D26A variant was found to have only 10% of the activity of wild-type Trx-(SH) 2 toward reducing insulin disulfides. The inclusion of exogenous bases substantially increased the activities of D26N-Trx and D26L-Trx in the reduction of 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB). The intermolecular interactions between EcTrx and its substrate proteins leads to high affinity and substrate specificity, resulting in ∼10 4-fold enhanced rates for both the oxidation and reduction reactions at neutral pH, as compared to similar reactions with small molecule thiols and unstrained disulfides. The computational analysis indicated that the surface of EcTrx and of chloroplast Trx-m had large negatively charged areas that were absent in Trx-f.

引用

页码：5768 / 5783

页数：16