Multiple functions of PDI. (A) PDI is an oxidoreductase that can both form (oxidase) and cleave (reductase) disulfide bonds. Active site cysteines are shown in red. Note that the catalytic cysteines are either reduced or oxidized during these processes. (B) Through its oxidoreductase activity, PDI acts as an isomerase changing disulfide bond patterns within a protein. In this example, PDI modifies disulfides formed between cysteines 1-2 and 3-4 into disulfides formed between 1-3 and 2-4 (numbering in red). Note that there is no net change in the redox state of the catalytic cysteines on PDI. (C) PDI can act as a chaperone, modifying the conformation of a protein independent of its oxidoreductase and chaperone activities. The redox state of the catalytic cysteines is unchanged. (D) The active site cysteines within PDI can also become S-nitrosylated. PDI can then transfer NO to substrates, thus acting as a nitrosylase. PDI can also act as a denitrosylase, removing NO from substrates. S-nitrosylation typically inactivates substrates, whereas denitrosylation activates substrates.