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Published on: July 27, 2022
Protein interactions of dirhodium tetraacetate: a structural study
Giarita Ferraro1, Alessandro Pratesi2, Luigi Messori1
1Department of Chemistry "Ugo Schiff", University of Florence, via della Lastruccia, 3-13, 50019, Sesto Fiorentino, Florence, Italy. luigi.messori@unifi.it.
The cytotoxic dirhodium complex [Rh2(μ-O2CCH3)4] binds to ribonuclease A (RNase A) by coordinating to a histidine side chain. This interaction is crucial for designing novel dirhodium-based metalloenzymes.
Area of Science:
- Bioinorganic Chemistry
- Protein-Metal Interactions
- Structural Biology
Background:
- Cytotoxic dirhodium complexes are promising therapeutic agents.
- Understanding protein-metal interactions is key to developing metalloenzymes.
Purpose of the Study:
- To investigate the binding interactions between a paddlewheel dirhodium complex and a model protein.
- To elucidate the binding mechanism at the molecular level.
Main Methods:
- High-resolution mass spectrometry
- X-ray crystallography
Main Results:
- The dirhodium complex [Rh2(μ-O2CCH3)4] extensively reacts with bovine pancreatic ribonuclease A (RNase A).
- Binding occurs through coordination of a histidine imidazole ring to an axial site of the dirhodium center.
- The dirhodium core and acetato ligands remain intact upon binding.
Conclusions:
- The study reveals a specific binding mode between the dirhodium complex and RNase A.
- These findings offer insights for the rational design of artificial dirhodium-containing metalloenzymes.
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