Inhibition of Thermus thermophilus HB8 thioredoxin activity by platinum(II).

A 1:1 thioredoxin-Pt(bpy) complex was prepared by adding [Pt(bpy)(en)]Cl(2)(bpy = 2,2'-bipyridine, en = ethylenediamine) to Thermus thermophilus HB8 thioredoxin in pH 8 phosphate buffer. Matrix-assisted laser desorption-ionization time of flight mass spectrometry (MALDI-TOF MS) and UV spectra of indicate the formation of Pt(bpy)(cys-Ala-Pro-cys-containing peptide fragment). These findings suggest that the Pt(bpy)(2+) unit binds to the active site of thioredoxin. The thioredoxin-platinum complex has no catalytic activity for the reduction of glutathione disulfide in the presence of NADPH and thioredoxin reductase, so that the platinum complex functions as an inhibitor.