Background
Nitric oxide (NO) signalling through activation of soluble guanylyl cyclase (sGC) is key for the physiology of the cardiovascular and neuronal systems. Discrepancies in sGC activation and deactivation in vitro vs. in vivo have led to a search for endogenous factors that regulate sGC or assist in cellular localization. In our previous work, which identified Hsp70 as a modulator of sGC, we determined that protein disulfide isomerase (PDI) bound to an sGC-affinity matrix [1]. As several studies have reported that thiol oxidants and reductants modulate sGC activity, we sought to characterize the potential interaction between sGC and PDI, an enzyme that not only isomerases disulfide bonds but also regulates some proteins activity via interaction with its cysteine (Cys) active sites [2, 3].