¹Department of Chemistry, Stanford University
²Department of Chemistry, Umeå University
³Stanford Synchrotron Radiation Lightsource

Cisplatin (cis-diamminedichloroplatinum(II)) is one of the most widely used anticancer drugs and is effective against several types of cancer tumors. The efficacy of cisplatin, however, is sometimes limited due to resistance mechanisms. It has been reported that Cu transporting proteins, such as Cu transporter 1 and Cu transporting ATPase ATP7A/B, are involved in cisplatin transfer across membranes to contribute to drug resistance. Human copper chaperone Atox1 maintains cellular Cu homeostasis by delivering Cu(I) and its metal site is structurally similar to metal-binding domains of ATP7A/B. Recent circular dichroism spectroscopy study has showed that cisplatin binds to Atox1 regardless of presence of Cu and has suggested that Cu and Pt are present in close proximity around the metal site of Atox1. In this study, the metal-site structure of cisplatin bound Atox1 has been investigated by X-ray absorption spectroscopy (XAS). The results of Cu K-edge and Pt L₃-edge XAS are very similar between cisplatin-added Cu-Atox1 and cisplatin-free Cu-Atox1 and between cisplatin-added Cu-Atox1 and cisplatin-added apo-Atox1, respectively. This suggests that there is no direct interaction between Cu and Pt in cisplatin bound Atox1 and that further analysis is required to exactly model the environments of Cu and Pt in this system.

https://conf-slac.stanford.edu/ssrl-lcls-2013/sites/conf-slac.stanford.e...