FIGURE 4.

The Cd-MsrA active site shows the first disulfide bond of the relay mechanism and a cacodylate molecule mimicking the substrate. A, the Cd-MsrA active site shows that Cys⁵² and Cys²⁰⁶ can both be in the reduced form, as in a disulfide bond state. Furthermore, a cacodylate molecule, shown in a purple stick representation, forms hydrogen bonds with Tyr⁸³, Glu⁹⁵, and Tyr¹³⁵ and interacts with Asp¹³⁰ via a water molecule. The two methyl groups of the cacodylate molecule are oriented toward the hydrophobic pocket composed of Tyr⁵³ and Trp⁵⁴, on the other side of the active site. The Cys⁵², Tyr⁵³, Trp⁵⁴, Tyr⁸³, Glu⁹⁵, Asp¹³⁰, Tyr¹³⁵, and Cys²⁰⁶ residues are shown in stick representation. B, the electron density around Cys⁵² and Cys²⁰⁶ is shown at 1.2σ contour level. C, the N. meningitidis MsrA (Protein Data Bank code 3BQF) active site shows stabilization interactions between the substrate, Ac-Met-S-SO-NHMe (shown in a yellow stick representation), and the conserved hydrogen bond donors Tyr⁸², Glu⁹⁴, and Tyr¹³⁴. These residues, as well as Phe⁵² and Trp⁵³, are shown in a green stick representation. D, the disulfide bond between Cys⁵² and Cys²⁰⁶ is not surface-exposed. Cd-MsrA is shown in a gray surface representation, whereas Cys⁵² and Cys²⁰⁶ are shown in a green stick representation. The figures were generated using MacPyMol (Schroedinger, LLC).