## 1 Introduction  
The classical anticancer platinum agents, such as cisplatin [_cis_-diamminedichloroplatinum (II)], transplatin [_trans_-diamminedichloroplatinum (II)] and oxaliplatin [1,2-diaminocyclohexane-oxalateplatinum (II)], were used widely in clinical therapy effectively against several common types of tumors [1, 2, 3, 4, 5, 6], such as ovarian, testicular and lung cancer tumors. The mechanism of the platinum agents against tumor is thought to be that the Pt (II) center attacks DNA through the contacts of covalent bonds with the N7 atoms of guanines of the DNA molecule in order to prevent the replication and transcription of DNA, consequently to lead to the cell apoptosis [7, 8, 9, 10]. In cancer treatment, the platinum agents transiting the nuclear membranes and reacting with DNA play a key role in improving the therapeutic efficacy. However, the efficacy of these platinum agents is restricted by the reduced uptake to the cytoplasm and increased efflux, consequently decreasing the possibility of the DNA target. In fact, the platinum agents can react rapidly with some macromolecules in the cytoplasm, especially thiol compounds, and become invalid before entering cell nucleus [11, 12]. Therefore, the studies on the resistance mechanism of the platinum agents and the interactions between the platinum agents and the biomacromolecules have become a hot topic in recent years. To date, many studies have proposed that copper (Cu) transporting proteins are related with both uptake and efflux of platinum agents in the cytoplasm [13, 14, 15, 16]. For example, it has been reported that the copper transporter 1 (Ctrl) protein, one of the copper influx transporting proteins, is responsible for platinum agent uptake [17, 18], whereas the copper transporting ATPases ATP7A and ATP7B proteins (the Menkes and Wilson disease proteins, respectively) are involved in the platinum agent efflux from cell [19, 20]. Each of the ATP7A and ATP7B proteins has six \(N\)-terminal metal-binding domains (MBDs) with similar structures. Each metal-binding domain has a ferredoxin like fold and a conserved metal-binding site, MetX\({}_{1}\)CysX\({}_{2}\)X\({}_{3}\)Cys (\(X_{i}\) = any residue), in a solvent-exposed loop, which contributes to the metal transporting. Interestingly, the NMR solution structure of the chaperone Atox1 (antioxidant-1) protein reported by [PERSON] and co-workers in 2004 presented that this protein also has a ferredoxin like fold and a conserved metal-binding site, the structures of which are similar to those in the ATP7A and ATP7B proteins [21]. Therefore, the Atox1 protein is thought to be a metal transporting protein, and be able to interact with the platinum agent to influence its accumulation in the cytoplasm. The studies of the Atox1 mutations in mice reported by [PERSON] and co-workers suggested that the Atox1 protein can bind to the cisplatin agent [22]. Subsequently, the X-ray crystal structures of the cisplatin agent + Atox1 protein complexes were reported by [PERSON] and co-workers in 2009 [23], which present the combination of a platinum agent with an Atox1 protein or an Atox1 dimer. The Atox1 protein with 68 residues consists of a compact \(\beta\)1\(\alpha\)1\(\beta\)2\(\beta\)3\(\alpha\)2\(\beta\)4 structure with the conserved metal-binding sites, Met10 Thr11 Cys12 Gly13 Gly14 Cys15, located at the solvent-exposed \(\beta\)1-\(\alpha\)1 loop that is a linker of the \(\beta\)1 strand and the \(\alpha\)1 helix. The binary complex is composed by a single Atox1 protein and a platinum ion that is coordinated by two S atoms of Cys12 and Cys15 at the metal-binding sites of the Atox1 protein [23]. In the ternary structure, the two Atox1 proteins are linked by the platinum center of the cisplatin agent at the same binding sites of residues Cys15 [23]. In addition, the NMR experimental results reported by [PERSON] and co-workers presented that the cisplatin + Atox1 derivative could be characterized by having a slightly strained chelate ring, affording a free position for sequential binding of an Atox1 protein [24].