Dirhodium Tetraacetate Binding to Lysozyme at Body Temperature

Area of Science:

• Biochemistry
• Materials Science
• Crystallography

Background:

• Paddlewheel dirhodium complexes are cytotoxic and used in catalysis and artificial metalloenzymes.
• Dirhodium tetraacetate ([Rh2(μ-O2CCH3)4]) reacts with hen egg white lysozyme (HEWL), forming adducts with both dimeric and monometallic rhodium fragments.
• Previous studies determined low-temperature structures of these adducts.

Purpose of the Study:

• To investigate the reaction and binding of dirhodium tetraacetate ([Rh2(μ-O2CCH3)4]) with hen egg white lysozyme (HEWL) at body temperature (37 °C).
• To compare the protein-metal adduct structures formed at different temperatures.

Main Methods:

• X-ray diffraction was used to analyze crystals of HEWL soaked with dirhodium tetraacetate at 37 °C.
• Crystals were grown and treated under conditions mimicking physiological temperature and buffer environments.
• Structures were compared to those obtained at lower temperatures (20 °C).

Main Results:

• Dirhodium tetraacetate ([Rh2(μ-O2CCH3)4]) reacts with HEWL at 37 °C, confirming binding occurs at body temperature.
• The overall structures of the Rh/HEWL adducts are similar at 20 °C and 37 °C, with conserved metal binding sites.
• Higher metal-containing fragment occupancy was observed in the structure formed at 37 °C.

Conclusions:

• Temperature plays a role in the protein metalation process by dirhodium complexes.
• The findings suggest that dirhodium complexes can interact with proteins under physiological conditions.
• This research provides insights into the behavior of metallodrugs and catalysts in biological systems at body temperature.