DUB Inhibitors - How do they work? (Apr/19/2010 )

Hi all. Does anyone know of a good paper that explains the mechanism of how N-ethylmaleimide NEM inhibits Deubiquitinases or DUBs? Thanks.

NEM permanently, covalently modifies free cysteine residues (those not involved in disulfide bonds and those not deeply embedded in a folded protein). This blocks the DUB active sites... Unfortunately, NEM modifies ALL free cysteines, so while it deactivates DUBs, it also screws with all the other proteins in the cell which have free cysteines... including the one you might be trying to study. It's a sledge-hammer of an "inhibitor".