Identification of platination sites on human serum transferrin using 13C and 15N NMR spectroscopy

被引:68
作者
Cox, MC
Barnham, KJ
Frenkiel, TA
Hoeschele, JD
Mason, AB
He, QY
Woodworth, RC
Sadler, PJ
机构
[1] Univ Edinburgh, Dept Chem, Edinburgh EH9 3JJ, Midlothian, Scotland
[2] Natl Inst Med Res, Biomed NMR Ctr, London NW7 1AA, England
[3] Michigan State Univ, Dept Chem, E Lansing, MI 48824 USA
[4] Univ Vermont, Coll Med, Dept Biochem, Burlington, VT 05405 USA
来源
JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY | 1999年 / 4卷 / 05期
关键词
transferrin; platinum; anticancer complexes; NMR spectroscopy; methionine;
D O I
10.1007/s007750050386
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Reactions between various apo and metal-bound forms of human serum transferrin (80 kDa) and the recombinant N-lobe (40 kDa) with [Pt(en)Cl-2] or cis-[PtCl2(NH3)(2)] have been investigated in solution via observation of [H-1,N-15] NMR resonances of the Pt complexes, [H-1,C-13] resonances of the epsilon CH3 groups of the protein methionine residues, and by chromatographic analysis of single-site methionine mutants. For the whole protein, the preferred Pt binding site appears to be Met256. Additional binding occurs at the other surface-exposed methionine (Met499), which is platinated at a slower rate than Met256. In contrast, binding of similar Pt compounds to the N-lobe of the protein occurs at Met313, rather than Met256. Met313 is buried in the interlobe contact region of intact transferrin. After loss of one chloride ligand from Pt and binding to methionine sulfur of the N-lobe, chelate-ring closure appears to occur with binding to a deprotonated backbone amide nitrogen, and the loss of the other chloride ligand. Such chelate-ring closure was not observed during reactions of the whole protein, even after several days.
引用
收藏
页码:621 / 631
页数:11
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