title: Identification of binding sites of cisplatin to human copper chaperone protein Cox17 by high-resolution FT-ICR-MS.
abstract: Cox17 is a key copper chaperone protein responsible for delivery of cuprous ions to mitochondria and has been demonstrated to be involved in the anticancer action of cisplatin. However, the binding sites of the drug to the protein have not yet been directly identified.
  
  
  
  The recombinant protein apo-Cox172s-s , the functional state of Cox17 transferring Cu(I), was reacted with an excess of cisplatin to produce platinated Cox17 adducts, of which the platination sites were identified by high-resolution Fourier transform ion cyclotron tandem mass spectrometry (FT-ICR-MS/MS) through electron capture dissociation (ECD).
  
  
  
  Primary FT-ICR-MS showed that mono-platinated Cox17 adducts were the main products, and top-down MS/MS results indicated that cisplatin bound to the Cys26 or Cys27 residue which is the binding site of cuprous ions in apo-Cox172s-s .
  
  
  
  This is the first report for identification of the main binding sites of cisplatin to Cox17 by top-down high-resolution mass spectrometry, providing direct evidence for the competitive coordination with Cox17 of cisplatin and cuprous ions. These findings will also be helpful to understand further how Cox17 facilitates cisplatin accumulation in mitochondria, and how cisplatin disturbs the transportation of cuprous ions. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: School of Chemical and Environmental Engineering, China University of Mining and Technology, Beijing, 100083, China.|Beijing National Laboratory for Molecular Sciences; National Centre for Mass Spectrometry in Beijing; CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.
authors.forename: Lijie
authors.initials: L
authors.lastname: Li
authors.affiliation: Beijing National Laboratory for Molecular Sciences; National Centre for Mass Spectrometry in Beijing; CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.affiliation: Beijing National Laboratory for Molecular Sciences; National Centre for Mass Spectrometry in Beijing; CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.
authors.forename: Kui
authors.initials: K
authors.lastname: Wu
authors.affiliation: Beijing National Laboratory for Molecular Sciences; National Centre for Mass Spectrometry in Beijing; CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Beijing National Laboratory for Molecular Sciences; National Centre for Mass Spectrometry in Beijing; CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Luo
authors.affiliation: School of Chemical and Environmental Engineering, China University of Mining and Technology, Beijing, 100083, China.
authors.forename: Qingwu
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Beijing National Laboratory for Molecular Sciences; National Centre for Mass Spectrometry in Beijing; CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.
authors.forename: Jianan
authors.initials: J
authors.lastname: Liu
authors.affiliation: Beijing National Laboratory for Molecular Sciences; National Centre for Mass Spectrometry in Beijing; CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.
authors.forename: Shaoxiang
authors.initials: S
authors.lastname: Xiong
authors.affiliation: Beijing National Laboratory for Molecular Sciences; National Centre for Mass Spectrometry in Beijing; CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.
authors.forename: Fuyi
authors.initials: F
authors.lastname: Wang
mesh_terms: D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002945:Cisplatin / Q000737:chemistry / Q000378:metabolism*; D000079922:Copper Transport Proteins; D005583:Fourier Analysis; D006801:Humans; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: C491006:COX17 protein, human; D002352:Carrier Proteins; D000079922:Copper Transport Proteins; D002945:Cisplatin