Premium
Bacitracin is not a specific inhibitor of protein disulfide isomerase
Author(s) -
Karala AnnaRiikka,
Ruddock Lloyd W.
Publication year - 2010
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2010.07660.x
Subject(s) - bacitracin , protein disulfide isomerase , in vivo , biochemistry , protein folding , chemistry , in vitro , chaperone (clinical) , isomerase , enzyme , biology , medicine , microbiology and biotechnology , pathology , antibiotics
To successfully dissect molecular pathways in vivo , there is often a need to use specific inhibitors. Bacitracin is very widely used as an inhibitor of protein disulfide isomerase (PDI) in vivo . However, the specificity of action of an inhibitor for a protein‐folding catalyst cannot be determined in vivo . Furthermore, in vitro evidence for the specificity of bacitracin for PDI is scarce, and the mechanism of inhibition is unknown. Here, we present in vitro data showing that 1 m m bacitracin has no significant effect on the ability of PDI to introduce or isomerize disulfide bonds in a folding protein or on its ability to act as a chaperone. Where bacitracin has an effect on PDI activity, the effect is relatively minor and appears to be via competition of substrate binding. Whereas 1 m m bacitracin has minimal effects on PDI, it has significant effects on both noncatalyzed protein folding and on other molecular chaperones. These results suggest that the use of bacitracin as a specific inhibitor of PDI in cellular systems requires urgent re‐evaluation.