Figure 1 - full size

 

Figure 1.
Structural effects of mutations designed to test the hypothesis that Cys^106-sulfinic acid formation is critical to DJ-1 function. A, a ribbon representation of the DJ-1 dimer, with one monomer in brown and the other in green. The dimer 2-fold axis is perpendicular to the page and indicated by an ellipse. The oxidationprone cysteine (C106) and the interacting glutamic acid (E18) are represented in each monomer. B, electron density for the 1.15 Å resolution structure of E18Q DJ-1 around Cys^106 is shown at the 1σ contour level and calculated with σ[A] weighted coefficients 2mF[o] - DF[c]. In E18Q DJ-1, Cys^106 is oxidized to the cysteine-sulfinic acid, where stabilizing hydrogen bonds are shown as dotted lines with distances given in Å. C, a superposition of oxidized E18Q (darker model) and wild-type DJ-1 (lighter model) shows that the key stabilizing hydrogen bond between residue 18 and Cys^106- is lengthened in E18Q DJ-1, weakening this interaction. D, 2mF[o] - DF[c] electron density contoured at 1σ is shown in blue for the 1.20 Å resolution crystal structure of E18D DJ-1. Cys^106 is oxidized to the easily reduced Cys^106-SO^- oxidation product in this variant. In addition, there is minor electron density that is consistent with either Cys^106- or an alternate conformation for Cys^106-SO^-. E, a superposition of residues in the vicinity of Cys^106 in E18D DJ-1 (darker model) and the corresponding region in oxidized wild-type DJ-1 (lighter model). The E18D substitution results in structural perturbations at Cys^106 that stabilize the Cys^106-SO^- oxidation product and hinder further oxidation. All figures were created using POVscript+ (40).

The above figure is reprinted by permission from the ASBMB: J Biol Chem (2009, 284, 6476-6485) copyright 2009.