title: Inhibition of Thermus thermophilus HB8 thioredoxin activity by platinum(II).
abstract: 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.
authors.affiliation: Department of Macromolecular Science, Graduate School of Science, Osaka University, Toyonaka, Osaka 560-0043, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kato
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Taka-aki
authors.initials: TA
authors.lastname: Okamura
authors.forename: Nobuko
authors.initials: N
authors.lastname: Maoka
authors.forename: Ryoji
authors.initials: R
authors.lastname: Masui
authors.forename: Seiki
authors.initials: S
authors.lastname: Kuramitsu
authors.forename: Norikazu
authors.initials: N
authors.lastname: Ueyama
mesh_terms: 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
chemical_list: D009944:Organoplatinum Compounds; D013879:Thioredoxins; D009249:NADP; D013880:Thioredoxin-Disulfide Reductase; D019803:Glutathione Disulfide