CRYSTAL-STRUCTURE OF THE CYANIDE-INHIBITED XENOPUS-LAEVIS CU,ZN SUPEROXIDE-DISMUTASE AT 98-K

The crystal structure of cyanide-inhibited X. laevis Cu,Zn superoxide dismutase has been studied and refined based on diffraction data collected at 98 K. The final R-factor for the 27,299 reflections in the 10.0-1.7 Angstrom resolution range is 0.170. The cyanide anion, which is a competitive inhibitor expected to mimic the superoxide binding mode, binds directly to the active site copper atom, replacing the coordinated water molecule. Moreover, the anion establishes a strong electrostatic interaction with the guanidinium group of the conserved active site residue Arg(141). The coordination sphere of Cu2+ is partly altered with respect to the uninhibited enzyme: a displacement of 0.41 Angstrom in subunit A, and 0.27 Angstrom in subunit B of the dimeric enzyme is observed for the Cu2+ ions. Only two ligands in the Cu2+ coordination sphere (His(46)and His(118)) are significantly affected by cyanide binding, whereas virtually no rearrangement of the Zn2+ ligands is reported.