Abstract
The so called “copper trafficking system” in mammalian cells is primarily devoted to the regulation of copper transport and homeostasis. This system, now well characterized, consists of a few strictly interconnected proteins that assist copper entrance inside cells and then promote metal transfer and delivery to essential copper-dependent cellular proteins (Boal and Rosenzweig 2009a; Banci et al., Mol Life Sci 67:2563–2589, 2010). Yet, the “copper trafficking system” may also facilitate the entrance inside cells of non-physiological metal species such as clinically established platinum drugs. ESI and MALDI MS methods are exploited here to characterize the interactions occurring between the experimental anticancer organogold(III) drug, Aubipyc, and the copper chaperone Atox1, a key protein of the copper trafficking system. The nature of the adducts that are formed when reacting Aubipyc with Atox1 is elucidated in detail. Characterization of the Aubipyc/Atox1 system is further supported by circular dichroism experiments. Binding competitions with mercury and bismuth ions were also explored. The relevance and the biological implications of the present results are discussed.
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Acknowledgments
This work was supported by Beneficentia Stiftung (Vaduz, Liechtenstein), AIRC (IG-16049), CIRCMSB and Cost Action CM1105. CG and GP acknowledge University of Pisa for PRA2015-0055 Grant.
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Marzo, T., Scaletti, F., Michelucci, E. et al. Interactions of the organogold(III) compound Aubipyc with the copper chaperone Atox1: a joint mass spectrometry and circular dichroism investigation. Biometals 28, 1079–1085 (2015). https://doi.org/10.1007/s10534-015-9887-z
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DOI: https://doi.org/10.1007/s10534-015-9887-z