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Interactions of platinum complexes with thioltransferase(glutaredoxin), in vitro
W W Wells1, P A Rocque, D P Xu
1Department of Biochemistry, Michigan State University, East Lansing 48824.
Biochemical and Biophysical Research Communications
|October 31, 1991
Summary
Platinum drugs like cisplatin inhibit thioltransferase (glutaredoxin) activity. Cisplatin and carboplatin strongly inhibit this enzyme, affecting its structure by forming dimers and trimers.
Area of Science:
- Biochemistry
- Enzymology
- Pharmacology
Background:
- Thioltransferase (glutaredoxin) is a key enzyme in cellular redox homeostasis.
- Platinum-based drugs are widely used in cancer chemotherapy.
Purpose of the Study:
- To investigate the in vitro inhibitory effects of platinum-based drugs on pig liver thioltransferase (glutaredoxin).
- To characterize the interaction between platinum drugs and thioltransferase under different conditions.
Main Methods:
- Enzyme inhibition assays using recombinant pig liver thioltransferase.
- Treatment with cisplatin, carboplatin, and transplatin under anaerobic and aerobic conditions.
- Analysis of enzyme structure changes (monomer, dimer, trimer formation) using incubation studies.
Main Results:
- Strong inhibition of thioltransferase by cisplatin and carboplatin under anaerobic conditions, with approximate 1:1 drug-to-enzyme ratios for total inhibition.
- Transplatin showed less sensitivity compared to cisplatin and carboplatin.
- High drug concentrations and aerobic conditions led to thioltransferase monomer cross-linking into dimers and trimers, particularly with cisplatin.
Conclusions:
- Platinum drugs, especially cisplatin and carboplatin, can potently inhibit thioltransferase (glutaredoxin) activity.
- The interaction involves direct binding and can lead to structural alterations of the enzyme.
- These findings suggest a potential mechanism for platinum drug action involving enzyme inhibition and structural modification.