The reaction of a platinated methionine motif of CTR1 with cysteine and histidine is dependent upon the type of precursor platinum complex.

The reaction of a platinated methionine motif of CTR1 with cysteine and histidine is dependent upon the type of precursor platinum complex.
J Inorg Biochem. 2015 Jul 21;
Authors: Ma G, Wu Q, Wu X, Arnesano F, Natile G, Sletten E, Liu Y
Abstract
The human copper protein (hCTR1) is believed to facilitate the cellular uptake of cisplatin. Cisplatin likely binds to the methionine (Met)-rich motifs located in the N-terminus of hCTR1, and ligand exchange would be essential if cisplatin has to pass through the hCTR1 channel. In this work, we investigated the reaction between platinated adducts of a methionine-rich motif of yeast CTR1 (Mets7) and N-acetyl-cysteine (AcCys) or N-acetyl-histidine (AcHis), mimicking metal-binding residues downstream the CTR1 channel. Platination involved two cis-compounds, cisplatin and oxaliplatin, and one monofunctional complex, cis-diammine(pyridine)chloridoplatinum(II) (cDPCP). The reactions were monitored by HPLC and the products were characterized by ESI-MS. The results indicate different reactivities depending upon the platinum complex. The cisplatin/Mets7 adduct reacts readily with both cysteine and histidine (t1/2<2min). In contrast, the oxaliplatin/Mets7 adduct reacts with cysteine but not with histidine, whereas cDPCP/Mets7 adduct reacts with histidine but not with cysteine. Hence, Mets7 adducts of these platinum complexes exhibit different reactivities towards downstream coordinating amino acids. ...

Source: Journal of Inorganic Biochemistry - July 21, 2015 Category: Biochemistry Authors: Ma G, Wu Q, Wu X, Arnesano F, Natile G, Sletten E, Liu Y Tags: J Inorg Biochem Source Type: research