Crystal structures of cisplatin bound to a human copper chaperone.
Copper trafficking proteins, including the chaperone Atox1 and the P(1B)-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.
Boal
Amie K
AK
Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois 60208, USA.
Rosenzweig
Amy C
AC
D001665:Binding Sites; D027682:Cation Transport Proteins / Q000737:chemistry*; D002945:Cisplatin / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D000079922:Copper Transport Proteins; D018360:Crystallography, X-Ray; D006801:Humans; D056511:Metallochaperones; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry*
C474500:ATOX1 protein, human; D027682:Cation Transport Proteins; D000079922:Copper Transport Proteins; D056511:Metallochaperones; D018832:Molecular Chaperones; D003300:Copper; D002945:Cisplatin