Crystal structures of cisplatin bound to a human copper chaperone.

Crystal structures of cisplatin bound to a human copper chaperone.
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DOI:
10.1021/ja906363t
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发表时间:
2009-10-14
影响因子:
15
通讯作者:
Rosenzweig AC
Rosenzweig AC
中科院分区:
化学1区
文献类型:
--
作者:
Boal AK;Rosenzweig AC

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铜运输蛋白,包括伴侣 Atox1 和 P1B 型 ATP 酶 ATP7B,与细胞对抗癌药物顺铂的耐药性有关。我们确定了顺铂-Atox1 加合物的两种晶体结构,揭示了保守的 CXXC 铜结合基序的铂配位。顺铂与这个功能相关位点的直接相互作用对于理解铜转运途径介导的耐药性的分子基础具有重要意义。
Copper trafficking proteins, including the chaperone Atox1 and the P1B-type ATPase ATP7B, have been implicated in cellular resistance to the anticancer drug cisplatin. We have determined two crystal structures of cisplatin-Atox1 adducts that reveal platinum coordination by the conserved CXXC copper-binding motif. Direct interaction of cisplatin with this functionally relevant site has significant implications for understanding the molecular basis for resistance mediated by copper transport pathways.
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