Structural model of the Vaccinia virus phosphatase, VH1 (pdb 3CM3) in the act of dephosphorylating activated STAT1 (pdb 1BF5). Surface representation of the dimeric phosphatase VH1 modeled in the act of dephosphorylating phosphorylated STAT1 core (in gray and orange, respectively). Ribbon diagram of VH1 and phosphorylated STAT1 are overlaid to their surface. The two active sites within VH1 are spaced 39Å apart. STAT1 flexible moiety connecting phosphorylated Tyr701 to the SH3 domains is modeled as a black dashed line; the two phosphorylated Tyr701 (shown in red) are modeled inside each of VH1 active sites. It is intriguing to speculate that VH1 specificity for activated STAT1 may be mediated by a dimeric quaternary structure. Accordingly, VH1 positions two active sites in the correct three-dimensional complementarity to recognize and dephosphorylate activated STAT1.
Nardozzi et al. Cell Communication and Signaling 2010 8:32 doi:10.1186/1478-811X-8-32