The hard path towards accurately measuring in vivo enzyme activity: the case of protein disulfide isomerase

by Denise C. Fernandes

Correct protein folding is a vital and extremely regulated cellular function. Disulfide bonds are essential determinants of the correctly folded protein structure. During the folding of nascent proteins into the endoplasmic reticulum (ER) lumen, essential enzymes promote disulfide bond insertion (oxidation) and their eventual repositioning (isomerization) when they are initially formed between wrong cysteines. These reactions are catalyzed by PDIs (protein disulfide isomerases), a family of enzymes that contains more than 20 members, from yeast to humans [1]. Thus, PDIs do not have one specific substrate, but rather a large variety of un/misfolded protein substrates.