A mass spectrometric comparison of the interactions of cisplatin and transplatin with myoglobin.
Mass spectrometric studies of the interactions of cisplatin and transplatin with myoglobin (Mb) provide information concerning interaction kinetics, Mb adduct identity, and cisplatin and transplatin binding sites on Mb. Although the Mb-cisplatin interaction is faster than the Mb-transplatin interaction, monoadducts and diadducts were formed in both the interactions over 30h. In order to locate the binding sites of cisplatin and transplatin on Mb, digests of free Mb, Mb-cisplatin and Mb-transplatin adducts were subjected to analysis by Fourier transform mass spectrometry (FT-MS). This analysis revealed that two fragment ions, 1313.27(5+) and 1316.68(5+), were obtained only from the Mb-cisplatin and Mb-transplatin adduct digests. Tandem mass spectrometry (MS/MS and MS(3)) of the 1313.27(5+) and 1316.68(5+) ions indicate that these ions arise from [Pt(NH(3))](2+) and [Pt(NH(3))(2)](2+), respectively, bound to peptide His97-Gly153. The product-ion spectra of the MS/MS and MS(3) analyses of the 1313.27(5+) ion indicate a common binding site of cisplatin and transplatin on His116-His119 residues. The interactions of cisplatin and transplatin with a dipeptide His-Ser and the three dimensional (3D) structure of native Mb suggest that cisplatin and transplatin coordinate to His116 and His119.
Zhao
Ting
T
C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, WV 26506-6045, USA.
King
Fred L
FL
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002945:Cisplatin / Q000737:chemistry* / Q000378:metabolism; D005583:Fourier Analysis; D006736:Horses; D007700:Kinetics; D013058:Mass Spectrometry / Q000379:methods*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009211:Myoglobin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry
D009211:Myoglobin; C034697:transplatin; D002945:Cisplatin