Catalysis of Disulfide Bond Formation by the Quiescin Sulfhydryl Oxidases
Published Online: 17 SEP 2012
Copyright © 2001 John Wiley & Sons, Ltd. All rights reserved.
How to Cite
Alon, A. and Fass, D. 2012. Catalysis of Disulfide Bond Formation by the Quiescin Sulfhydryl Oxidases. eLS. .
- Published Online: 17 SEP 2012
Quiescin sulfhydryl oxidase (QSOX), an enzyme that catalyses disulfide bond formation in the late secretory pathway and extracellular environment, is emerging as an important player in extracellular matrix assembly, with apparent physiological and pathological functions in development and cancer, respectively. High-resolution views into the QSOX catalytic machinery are providing information not only on the QSOX enzymes themselves but also on the larger protein disulfide isomerase family of oxidoreductases and on thioredoxin-fold superfamily proteins more generally. The two redox-active sites of QSOX are present within domains flexibly tethered to one another, but the sites cooperate tightly and productively to generate disulfide bonds de novo and transfer them to substrate proteins. Backbone and side-chain dynamics in the vicinity of the redox-active disulfides of QSOX enzymes appear to modulate the local electrostatics during catalysis, facilitating electron transfer in dithiol/disulfide exchange reactions.
QSOX enzymes accomplish both the generation of disulfides de novo and the delivery of disulfides to substrate proteins using a redox relay.
The amino (N)-terminal portion of QSOX is structurally and functionally similar to domains of protein disulfide isomerase family proteins.
The carboxy (C)-terminal portion of QSOX appears to have arisen by domain duplication and fusion from an Erv-family sulfhydryl oxidase precursor.
QSOX enzymes have structural features and appropriately positioned functional groups to enhance electron transfer between the two modules.
- disulfide bond formation;
- flavin adenine dinucleotide;
- oxidative protein folding;
- protein disulfide isomerase