Structural Biology of Cisplatin Complexes with Cellular Targets: The Adduct with Human Copper Chaperone Atox1 in Aqueous Solution

被引：17

作者：

Calandrini, Vania ^{[1
,2
,3
]}

Trung Hai Nguyen ^{[1
,2
,3
]}

Arnesano, Fabio ^{[4
]}

Galliani, Angela ^{[4
]}

Ippoliti, Emiliano ^{[1
,2
,3
]}

Carloni, Paolo ^{[1
,2
,3
]}

Natile, Giovanni ^{[4
]}

机构：

[1] German Res Sch Simulat Sci, D-52425 Julich, Germany

[2] Forschungszentrum Julich, Inst Adv Simulat IAS 5, D-52425 Julich, Germany

[3] Forschungszentrum Julich, Inst Neurosci & Med INM 9, D-52425 Julich, Germany

[4] Univ Bari A Moro, Dept Chem, I-70125 Bari, Italy

来源：

CHEMISTRY-A EUROPEAN JOURNAL | 2014年 / 20卷 / 37期

关键词：

cisplatin; computer chemistry; hybrid QM/MM simulations; NMR chemical shifts; molecular modeling; NMR CHEMICAL-SHIFTS; ORDER REGULAR APPROXIMATION; MOLECULAR-DYNAMICS; AB-INITIO; PLATINUM; PROTEIN; TRANSPORTERS; RECOGNITION; PHARMACOLOGY; SENSITIVITY;

D O I：

10.1002/chem.201402834

中图分类号：

O6 [化学];

学科分类号：

070301 [无机化学];

摘要：

Cisplatin is one of the most used anticancer drugs. Its cellular influx and delivery to target DNA may involve the copper chaperone Atox1 protein. Although the mode of binding is established by NMR spectroscopy measurements in solution-the Pt atom binds to Cys12 and Cys15 while retaining the two ammine groups-the structural determinants of the adduct are not known. Here a structural model by hybrid Car-Parrinello density functional theory-based QM/MM simulations is provided. The platinated site minimally modifies the fold of the protein. The calculated NMR and CD spectral properties are fully consistent with the experimental data. Our in silico/in vitro approach provides, together with previous studies, an unprecedented view into the structural biology of cisplatin-protein adducts.

引用

页码：11719 / 11725

页数：7

共 67 条

[1]

Toward reliable density functional methods without adjustable parameters: The PBE0 model [J].