Journal article

Interaction of cisplatin and analogues with a Met-rich protein site

Chak Ming Sze, George N Khairallah, Zhiguang Xiao, Paul S Donnelly, Richard AJ O'Hair, Anthony G Wedd

JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY | SPRINGER | Published : 2009

Abstract

The chaperone protein CopC from Pseudomonas syringae features high-affinity binding sites (K (D) ~ 10(-13) M) for both Cu(I) (Met-rich) and Cu(II) (His-rich). When presented with these sites in the apoprotein, electrospray ionisation mass spectrometry confirmed that cis-Pt(NH(3))(2)Cl(2) (cisplatin) and the fragments [Pt(II)L](2+) (L is 1,2-diaminoethane, 2,2'-bipyridine) occupied the Cu(I) site specifically in the 1:1 Pt-CopC adducts (purified by cation-exchange chromatography). The cis-Pt(NH(3))(2) fragment was not present in these adducts (the dominant product for cisplatin was Pt-CopC in which all original ligands were displaced), while bidentate ligands L were retained in LPt-CopC adduc..

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Grants

Awarded by Australian Research Council


Funding Acknowledgements

We thank the Australian Research Council for financial support under Grant A29930204 and Robert Borthwick for preliminary studies on the Pt(bpy)<SUP>2+</SUP> system. The Australian Research Council, together with the Victorian Institute for Chemical Sciences, is also thanked for funding the purchase of the LTQ Fourier transform mass spectrometer.