Structure-based functional motif identifies a potential disulfide oxidoreductase active site in the serine/threonine protein phosphatase-1 subfamily

In previous work, 3-dimensional descriptors of protein function ('fuzzy fun ctional forms') were used to identify disulfide oxidoreductase active sites in high-resolution protein structures. During this analysis, a potential d isulfide oxidoreductase active site in the serine/threonine protein phospha tase-1 (PP1) crystal structure was discovered. In PP1, the potential redox active site is located in close proximity to the phosphatase active site. T his result is interesting in view of literature suggesting that serine/thre onine phosphatases could be subject to redox control mechanisms within the cell; however, the actual source of this control is unknown. Additional ana lysis presented here shows that the putative oxidoreductase active site is highly conserved in the serine/threonine phosphatase-l subfamily, but not i n the serine/threonine phosphatase-2A or -2B subfamilies. These results dem onstrate the significant advantages of using structure-based motifs for pro tein functional site identification. First, a putative disulfide oxidoreduc tase active site has been identified in serine-threonine phosphatases using a descriptor built from the glutaredoxin/thioredoxin family, proteins that have no apparent evolutionary relationship whatsoever to the PPI proteins. Second, the proximity of the putative disulfide oxidoreductase active site to the phosphatase active site provides evidence toward a regulatory contr ol mechanism. No sequence-based method could provide either piece of inform ation.