標題: Protein-protein interaction as a powering source of oxidoreductive reactivity
作者: Lin, Tiao-Yin
生物科技學系
Department of Biological Science and Technology
公開日期: 2010
摘要: Thiol-disulfide exchange reactions between thiol-disulfide oxidoreductases (e. g. thioredoxin or Trx) and client proteins can obtain a rate several orders faster than those between chemical reagents (e. g. dithiothreitol) and client proteins. The active sites of these oxidoreductases are characterized by a CXXC motif. The XX dipeptide of Trx is GP. By altering the C-terminal X to A, K and D, it is shown that the P -> K mutation confers the largest effect on the redox potential, which it elevated by 28 mV, while the P -> D mutation displays the smallest variation. The change in pK(a) of the nucleophilic thiol also follows this trend. However, GK and GA react faster with thioredoxin reductase, exhibiting a rate rank of GK > GA > GP > GD, while the rates toward insulin and PDI follow the order GP > GA > GK > GD. The rate change spans two to three orders of magnitude. This work demonstrates that redox reactivity does not correlate simply with pK(a) and redox potential, but instead supports the important role of interaction between proteins in determining the fast reactivity and rate order of Trx. A reaction mechanism involving the transient formation of a Trx-protein binding complex is proposed for the oxidoreduction of protein thiols-disulfides. Furthermore, studies on insulin reduction show that Trx acts as an enzyme rather than a redox couple. These results provide explanations for the observed variations of the CXXC motif in PDI-like proteins as well as the conservation of the CXXC motif in Trx.
URI: http://hdl.handle.net/11536/6005
http://dx.doi.org/10.1039/b927132e
ISSN: 1742-206X
DOI: 10.1039/b927132e
期刊: MOLECULAR BIOSYSTEMS
Volume: 6
Issue: 8
起始頁: 1454
結束頁: 1462
Appears in Collections:Articles


Files in This Item:

  1. 000279914300016.pdf