Abstract
Protein disulfide isomerase (PDI) is a 57-kDa oxidoreductase that facilitates cysteine
thiol reactions inside and outside the cell. It mediates reduction or oxidation of
protein disulfide bonds, thiol/disulfide exchange reactions, and transfer of NO from
one protein thiol to another. It also has chaperone properties. PDI is actively secreted
by most, if not all, of the cell types involved in thrombosis, binds to integrins
on the cell surface, and circulates as a soluble protein in blood. It plays a critical
role in thrombosis in mice and presumably the same role in human thrombosis. Eight
proteins involved in thrombosis have been identified as PDI substrates; however, the
role of this oxidoreductase in this process is not fully understood. Novel small-molecule
PDI inhibitors have been developed and are being evaluated as antithrombotics in clinical
trials. This combination of ongoing laboratory and clinical studies will greatly accelerate
the pace of discovery and targeting of PDI function in thrombosis.
Keywords
thrombosis - protein disulfide isomerase - allosteric disulfides - antithrombotics
