FIGURE 1.

Structural effects of mutations designed to test the hypothesis that Cys¹⁰⁶-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 Cys¹⁰⁶ is shown at the 1σ contour level and calculated with σ_A weighted coefficients 2mF_o - DF_c. In E18Q DJ-1, Cys¹⁰⁶ 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 Cys¹⁰⁶- 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. Cys¹⁰⁶ is oxidized to the easily reduced Cys¹⁰⁶-SO^- oxidation product in this variant. In addition, there is minor electron density that is consistent with either Cys¹⁰⁶- or an alternate conformation for Cys¹⁰⁶-SO^-. E, a superposition of residues in the vicinity of Cys¹⁰⁶ 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 Cys¹⁰⁶ that stabilize the Cys¹⁰⁶-SO^- oxidation product and hinder further oxidation. All figures were created using POVscript+ (40).