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.
Kato
Masahiro
M
Department of Macromolecular Science, Graduate School of Science, Osaka University, Toyonaka, Osaka 560-0043, Japan.
Yamamoto
Hitoshi
H
Okamura
Taka-aki
TA
Maoka
Nobuko
N
Masui
Ryoji
R
Kuramitsu
Seiki
S
Ueyama
Norikazu
N
D001665:Binding Sites; D002384:Catalysis; D002942:Circular Dichroism / Q000379:methods; D019803:Glutathione Disulfide / Q000737:chemistry; D009249:NADP / Q000737:chemistry; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D013056:Spectrophotometry, Ultraviolet / Q000379:methods; D013329:Structure-Activity Relationship; D013880:Thioredoxin-Disulfide Reductase / Q000737:chemistry; D013879:Thioredoxins / Q000037:antagonists & inhibitors* / Q000737:chemistry
D009944:Organoplatinum Compounds; D013879:Thioredoxins; D009249:NADP; D013880:Thioredoxin-Disulfide Reductase; D019803:Glutathione Disulfide