A structure-based mechanism for copper-zinc superoxide dismutase

Area of Science:

• Biochemistry
• Structural Biology
• Enzymology

Background:

• Copper-zinc superoxide dismutase (CuZnSOD) is crucial for cellular defense against reactive oxygen species.
• Understanding the catalytic mechanism of CuZnSOD is essential for comprehending oxidative stress responses.

Purpose of the Study:

• To elucidate the reaction mechanism of yeast copper-zinc superoxide dismutase (CuZnSOD).
• To investigate structural changes in CuZnSOD under varying conditions, including oxygen pressure and azide binding.

Main Methods:

• X-ray crystallography was employed to determine three new structures of yeast CuZnSOD.
• Structures included wild type under 15 atm oxygen, wild type with azide, and a His48Cys mutant.

Main Results:

• Oxygen pressure and azide binding induce distinct copper ion displacements and coordination geometry changes.
• The His63 imidazole ring tilts, and the His48-copper bond elongates under these conditions.
• The His48Cys mutation results in a stable five-coordinate square pyramidal copper geometry with a chloride ligand.

Conclusions:

• A structure-based cyclic mechanism for CuZnSOD is proposed, incorporating inner and outer sphere electron transfer.
• Structural data supports a dynamic mechanism involving conformational changes in response to substrate and inhibitors.