Inactivation of dihydropteridine reductase (human brain) by platinum(II) complexes.
Potassium tetrachloroplatinate (K2PtCl4) inactivates dihydropteridine reductase from human brain in a time-dependent and irreversible manner. The inactivation has been followed by measuring enzyme activity and fluorescence changes. The enzyme is completely protected from inactivation by NADH, the pterin cofactor [quinonoid 6-methyl-7,8-dihydro(6H)pterin] and dithiothreitol. Evidence is presented that K2PtCl4 reacts at the active site and that (a) thiol group(s) is involved in, or is masked by, this reaction. K2PtCl4 is a stronger inhibitor of human brain dihydropteridine reductase that cis- and trans-diaminodichloroplatinum, cis-dichloro[ethylenediamine]platinum and K4Fe(CN)6, whereas H2PtCl6 is considerably weaker and (Ph3P)3RhCl is inactive.
D001665:Binding Sites; D001921:Brain / Q000201:enzymology; D002712:Chlorides / Q000494:pharmacology; D002945:Cisplatin / Q000494:pharmacology; D004093:Dihydropteridine Reductase / Q000037:antagonists & inhibitors*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors*; D009944:Organoplatinum Compounds / Q000494:pharmacology; D010984:Platinum / Q000494:pharmacology*; D017671:Platinum Compounds; D011487:Protein Conformation; D013050:Spectrometry, Fluorescence; D013438:Sulfhydryl Compounds
D002712:Chlorides; D009944:Organoplatinum Compounds; D017671:Platinum Compounds; D013438:Sulfhydryl Compounds; C036919:tetrachloroplatinate; C002892:platinum ethylenediamine dichloride; C034697:transplatin; D010984:Platinum; D004093:Dihydropteridine Reductase; D009247:NADH, NADPH Oxidoreductases; D002945:Cisplatin