NDLI: Copper binding modulates the platination of human copper chaperone Atox1 by antitumor trans-platinum complexes

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Metallomics Vol - 6 Issue - 2

Copper binding modulates the platination of human copper chaperone Atox1 by antitumor trans-platinum complexes

Content Provider	Royal Society of Chemistry (RSC)
Author	Tian, Changlin Guo, Wei Liu, Yangzhong Wang, Fuyi Xi, Zhaoyong
Copyright Year	2014
Abstract	The transport system of platinum-based anticancer agents is crucial for drug sensitivity. Increasing evidence indicates that the copper transport system is also involved in the cellular influx and efflux of platinum drugs. The copper chaperone Atox1 has been shown to bind to cisplatin in vitro and in cells. Previous results reveal that copper binding promotes the reaction between Atox1 and cisplatin. Here, we have performed detailed solution NMR and ESI-MS experiments to investigate the effect of Cu(I) binding on the reactions of Atox1 with two antitumor active trans-platinum agents, trans-EE and trans-PtTz. Results indicate that, similar to the reaction of cisplatin, copper coordination also enhances the platination of Atox1 by two trans-platinum complexes, and platinum binds to the copper coordinating residues. However, copper binding promotes the trans-platinum transfer from Atox1 to dithiothreitol (DTT). This result is in contrast to the reaction of Atox1 with cisplatin, in which the presence of copper largely suppresses the platination of DTT. Additionally, both apo- and CuI-Atox1 react faster with trans-platinum complexes than with cisplatin, however, less protein aggregation is observed in the reaction of trans-platinum complexes. These results indicate that the roles of Atox1 in the regulation of cellular trafficking of platinum drugs are dependent on the coordination configurations.
Starting Page	491
Ending Page	497
Page Count	7
File Format	HTM / HTML PDF
ISSN	17565901
Volume Number	6
Issue Number	3
Journal	Metallomics
DOI	10.1039/c3mt00338h
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	DTT Digital terrestrial television Nuclear magnetic resonance Copper Pharmacological chaperone Dithiothreitol Cisplatin Protein
Content Type	Text
Resource Type	Article
Subject	Chemistry Medicine Metals and Alloys Biochemistry Biomaterials Biophysics

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