Proton Sharing between Cysteine Thiols in Escherichia coli Thioredoxin: Implications for the Mechanism of Protein Disulfide Reduction

Mei Fen Jeng, Ame Holmgren, H. Jane Dyson

研究成果: Article同行評審

89 引文 斯高帕斯(Scopus)

摘要

Proton sharing between acidic groups has been observed in the active sites of several enzymes, including bacteriorhodopsin, aspartic proteases, and ribonuclease HI. We here report NMR observations suggestive of proton sharing between cysteine thiols in the active site of the oxidation-reduction enzyme thioredoxin. The pKas of the two cysteine thiols in the Escherichia coli protein are removed from the expected value of 8.4 by ~1 pH unit in either direction, upward and downward. Further, the Cβ resonances of both residues show clearly the effects of both of these pkas, indicating that the titrations of the two thiol groups are intimately linked. This behavior strongly suggests that the low pKa ascribed to the deprotonation of the Cys 32 thiol most likely arises through the interaction and close approach of the thiol of Cys 35, with the thiolate anion of Cys 32 stabilized through the sharing of the remaining thiol proton, nominally attached to Cys 35. These observations provide a rationale for the mediation of active site pH control, an important aspect of the mechanism of thioredoxin and other proteins with catalytic thioredoxin domains, such as protein disulfide isomerases.

原文English
頁(從 - 到)10101-10105
頁數5
期刊Biochemistry
34
發行號32
DOIs
出版狀態Published - 1995 八月

All Science Journal Classification (ASJC) codes

  • 生物化學

指紋

深入研究「Proton Sharing between Cysteine Thiols in Escherichia coli Thioredoxin: Implications for the Mechanism of Protein Disulfide Reduction」主題。共同形成了獨特的指紋。

引用此