title: Probing the interaction of cisplatin with cytochrome C by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry.
abstract: As one of the most important platinum drugs, the interactions of cisplatin with proteins play very important roles in its anticancer action and side effects. Here, the interaction of cisplatin with cytochrome c was investigated using Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS). On the basis of the high-resolution data, cytochrome c-Pt(NH(3))Cl was found to be the primary monoadduct. The platinated monoadducts were related to molar ratios of cytochrome c and cisplatin, and corresponding reaction pathways were proposed. Multiple binding sites of cisplatin on cytochrome c were directly determined by FTICR MS combined with trypsin digestion without liquid chromatography (LC) separation. Four binding sites (Met65, Met80, His18, and His33) for cisplatin on cytochrome c were identified. Moreover, hydrogen/deuterium exchange (H/DX) combined with FTICR MS provides the sensitive method to insight the small conformation change of cytochrome c induced by cisplatin. This strategy can be applied to comprehensive investigation of metallodrug/protein complexes.
authors: Changchun Center of Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, People's Republic of China.
authors: Ningbo
authors: N
authors: Zhang
authors: Yonggang
authors: Y
authors: Du
authors: Meng
authors: M
authors: Cui
authors: Junpeng
authors: J
authors: Xing
authors: Zhiqiang
authors: Z
authors: Liu
authors: Shuying
authors: S
authors: Liu
mesh_terms: D000818:Animals; D001665:Binding Sites; D002945:Cisplatin / Q000378:metabolism*; D017357:Cyclotrons; D045304:Cytochromes c / Q000737:chemistry / Q000378:metabolism*; D041961:Deuterium Exchange Measurement; D005583:Fourier Analysis; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D021241:Spectrometry, Mass, Electrospray Ionization / Q000295:instrumentation / Q000379:methods*
chemical_list: D010446:Peptide Fragments; D045304:Cytochromes c; D002945:Cisplatin