为什么二硫键异构酶A（DsbA）是一种氧化性如此强的二硫键催化剂？

Why is DsbA such an oxidizing disulfide catalyst?

作者信息

Grauschopf U, Winther J R, Korber P, Zander T, Dallinger P, Bardwell J C

机构信息

Universität Regensburg Institut für Biophysik und Physikalische Biochemie, Federal Republic of Germany.

出版信息

Cell. 1995 Dec 15;83(6):947-55. doi: 10.1016/0092-8674(95)90210-4.

DOI:10.1016/0092-8674(95)90210-4

PMID:8521518

Abstract

DsbA, a member of the thioredoxin family of disulfide oxidoreductases, acts in catalyzing disulfide bond formation by donating its disulfide to newly translocated proteins. We have found that the two central residues within the active site Cys-30-Pro-31-His-32-Cys-33 motif are critical in determining the exceptional oxidizing power of DsbA. Mutations that change these two residues can alter the equilibrium oxidation potential of DsbA by more than 1000-fold. A quantitative explanation for the very high redox potential of DsbA was found by measuring the pKa of a single residue, Cys-30. The pKa of Cys-30 varied dramatically from mutant to mutant and could accurately predict the oxidizing power of each DsbA mutant protein.

摘要

DsbA是二硫键氧化还原酶硫氧还蛋白家族的成员，通过将其二硫键提供给新转运的蛋白质来催化二硫键的形成。我们发现，活性位点Cys-30-Pro-31-His-32-Cys-33基序中的两个中心残基对于决定DsbA非凡的氧化能力至关重要。改变这两个残基的突变可使DsbA的平衡氧化电位改变超过1000倍。通过测量单个残基Cys-30的pKa，找到了对DsbA非常高的氧化还原电位的定量解释。Cys-30的pKa在不同突变体之间有很大差异，并且可以准确预测每个DsbA突变蛋白的氧化能力。