Li, Huilin, Lin, Tzu-Yung, Van Orden, Steve L., Zhao, Yao, (Researcher in chemistry), Barrow, Mark P., Pizarro, Ana M., Qi, Yulin, Sadler, P. J. and O’Connor, Peter B.. (2011) Use of top-down and bottom-up fourier transform ion cyclotron resonance mass spectrometry for mapping calmodulin sites modified by platinum anticancer drugs. Analytical Chemistry, Vol.83 (No.24). pp. 9507-9515. ISSN 0003-2700

Preview

Text WRAP_LI_477_Use of Top-down Fourier.pdf - Accepted Version Download (2295Kb) | Preview

Abstract

Calmodulin (CaM) is a highly conserved, ubiquitous, calcium-binding protein; it binds to and regulates many different protein targets, thereby functioning as a calcium sensor and signal transducer. CaM contains 9 methionine (Met), 1 histidine (His), 17 aspartic acid (Asp), and 23 glutamine acid (Glu) residues, all of which can potentially react with platinum compounds; thus, one-third of the CaM sequence is a possible binding target of platinum anticancer drugs, which represents a major challenge for identification of specific platinum modification sites. Here, top-down electron capture dissociation (ECD) was used to elucidate the transition metal–platinum(II) modification sites. By using a combination of top-down and bottom-up mass spectrometric (MS) approaches, 10 specific binding sites for mononuclear complexes, cisplatin and [Pt(dien)Cl]Cl, and dinuclear complex [{cis-PtCl2(NH3)}2(μ-NH2(CH2)4NH2)] on CaM were identified. High resolution MS of cisplatin-modified CaM revealed that cisplatin mainly targets Met residues in solution at low molar ratios of cisplatin–CaM (2:1), by cross-linking Met residues. At a high molar ratio of cisplatin:CaM (8:1), up to 10 platinum(II) bind to Met, Asp, and Glu residues. [{cis-PtCl2(NH3)}2(μ-NH2(CH2)4NH2)] forms mononuclear adducts with CaM. The alkanediamine linker between the two platinum centers dissociates due to a trans-labilization effect. [Pt(dien)Cl]Cl forms {Pt(dien)}2+ adducts with CaM, and the preferential binding sites were identified as Met51, Met71, Met72, His107, Met109, Met124, Met144, Met145, Glu45 or Glu47, and Asp122 or Glu123. The binding of these complexes to CaM, particularly when binding involves loss of all four original ligands, is largely irreversible which could result in their failure to reach the target DNA or be responsible for unwanted side-effects during chemotherapy. Additionally, the cross-linking of cisplatin to CaM might lead to the loss of the biological function of CaM or CaM–Ca2+ due to limiting the flexibility of the CaM or CaM–Ca2+ complex to recognize target proteins or blocking the binding region of target proteins to CaM.

Item Type:	Journal Article
Subjects:	Q Science > QD Chemistry Q Science > QP Physiology
Divisions:	Faculty of Science > Chemistry Faculty of Science > Engineering
Library of Congress Subject Headings (LCSH):	Antineoplastic agents, Calmodulin, Platinum compounds -- Therapeutic use, Fourier transform spectroscopy
Journal or Publication Title:	Analytical Chemistry
Publisher:	American Chemical Society
ISSN:	0003-2700
Date:	2011
Volume:	Vol.83
Number:	No.24
Page Range:	pp. 9507-9515
Identification Number:	10.1021/ac202267g
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Funder:	National Institutes of Health (U.S.) (NIH), European Research Council (ERC), Engineering and Physical Sciences Research Council (EPSRC)
Grant number:	NIH/NIGMSR01GM078293 (NIH), 247450 (ERC), EP/F034210/1 (EPSRC), BP/G006792 (EPSRC)
References:	1. Kelland, L. The resurgence of platinum-based cancer chemotherapy. Nat. Rev. Cancer. 2007, 7, 573-584. 2. Wang, X.; Guo, Z. The role of sulfur in platinum anticancer chemotherapy. Anti-cancer Agents in Med. Chem. 2007, 7, 19-34. 3. Cohen, S.; M.; Lippard S. J. Cisplatin: from DNA damage to cancer chemotherapy. Prog. Nucleic Acid Res. Mol. Biol. 2001, 67, 94-129. 4. Borst, P.; Rottenberg, S.; Jonkers, J. How do real tumors become resistant to cisplatin? Cell Circle. 2008, 7, 1353-1359. 5. Kroning, R.; Lichtenstein, A. K.; Nagami, G. T. Sufur-containing amino acids decrease cisplatin cytotoxicity and uptake in renal tubule epithelial cell lines. Cancer Chemother. Pharmacol. 2000, 45, 43-49. 6. Arnesano, F.; Boccarelli, A.; Cornacchia, D.; Nushi, F.; Sasanelli, R.; Coluccia, M.; Natile, G. Mechanistic insight into the inhibition of matrix metalloproteinase by platinum substrates. J. Med. Chem. 2009, 52, 7847-7855. 7. Karotki, A. V.; Vasak, M. Interaction of metallothionein-2 with platinum-modified 5’-guanosine monophosphate and DNA. Biochemistry. 2008, 47, 10961-10969. 8. Knipp, M. Karotki, A, V.; Chesnov, S.; Natile, G.; Sadler, P. J.; Brabec, V.; Vasak, M. Reaction of Zn7Metallothionein with cis- and trans-[Pt(N-donor)2Cl2] anticancer complexes: trans-PtII complexes retain their N-donor ligands. J. Med. Chem. 2007, 50, 4075-4086. 9. Lau, J. K.; Deubel, D. Loss of ammine from platinum(II) complexes: implications for cisplatin inactivation, storage, and resistance. Chem. Eur. J. 2005, 11, 2849-2855. 10. Crivici, A., and Ikura, M. Molecular and Structural Basis of Target Recognition by Calmodulin. Annu. ReV. Biophys. Biomol. Struct. 1995, 24, 85-116. 11. Nelson, M. R.; Chazin, W. J. An interaction-based analysis of calcium induced conformational changes in Ca 2+ sensor proteins. Protein Sci. 1998, 7, 270–282. 12. Vetter, S. W.; Leclerc, E. Novel aspects of calmodulin target recognition and activation. Eur. J. Biochem. 2003, 270, 404-414. 13. O’Neil, K. T.; DeGrado, W. F. How calmodulin binds its targets: sequence independent recognition of amphiphilic α-helices. Trends Biochem. Sci. 1990, 15, 59-64. 14. Gao, J.; Yin, D. H.; Yao, Y.; Sun, H.; Qin, Z.; Schoneich, C.; Williams, T. D.; Squier, T. C. Loss of conformational stability in calmodulin upon methionine oxidation. Biophysical J. 1998, 74, 1115-1134. 15. Bartlett, R. K.; Urbauer, R. J. B.; Anbanandam, A.; Smallwood, H. S.; Urbauer, J. L.; Squier, T. C. Oxidation of Met144 and Met145 in calmodulin blocks calmodulin dependent activation of the plasma membrane Ca-ATPase. Biochemistry. 2003, 42, 3231-3228. 16. Vougier, S.; Mary, J.; Dautin, N.; Vinh, J.; Friguet, B.; Ladant, D. Essential role of methionine residues in calmodulin binding to Bordetalla pertussis adenylate cyclase, as probed by selective oxidation and repair by the peptide methionine sulfoxide reductases. J. Biol. Chem. 2004, 279, 30210-30218. 17. Yao, Y.; Yin, D.; Jas, G. S.; Kuczera, K.; Williams, T. D.; Schoneih, C.; Squier, T. Oxidative modification of a carboxyl-terminal vicinal methionine in calmodulin by hydrogen peroxide inhibits calmodulin-dependent activation of the pasma membrane Ca-ATPase. Biochemistry. 1996, 35, 2767-2787. 18. Bigelow, D. J.; Squier, T. C. Redox modulation of cellular signaling and metabolism through reversible oxidation of methionine sensors in calcium regulatory proteins. Biochimica et Biophysica Acta. 2005, 1703, 121-134. 19. Jarve, R. K.; Aggarwal, S. K. Cisplatin-induced inhibition of the calcium-calmodulin complex, neuronal nitric oxide synthase activation and their role in stomach distention. Cancer Chemother. Pharmacol. 1997, 39, 341-348. 20. Car, S. A.; Annan, R. S. Overview of Peptide and Protein Analysis by Mass Spectrometry. Curr. Protoc. Mol. Biol. 1997, unit 10.21.1-10.21.27. 21. Zhao, T.; King, F. L. Direct determination of the primary binding site of cisplatin on cytochrome c by mass spectrometry. J. Am. Soc. Mass Spectrom. 2009, 20, 1141-1147. 22. Gibson, D.; Costello, C. E. A mass spectral study of the binding of the anticancer drug cisplatin to ubiquitin. Eur. Mass Spectrom. 1999, 5, 501-510. 23. Will, J.; Sheldrick,W. S. Characterization of cisplatin coordination sites in cellular Escherichia coli DNA-binding proteins by combined biphasic liquid chromatography and ESI tandem mass spectrometry. J. Biol. Inorg. Chem. 2008, 13, 421-434. 24. Allardyce, C. S.; Dyson, P. J.; Coffey, J.; Johnson, N. Determination of drug binding sites to proteins by electrospray ionisation mass spectrometry: the interaction of cisplatin with transferrin. Rapid Commun. Mass Spectrom. 2002, 16, 933–935. 25. Moreno-Gordaliza, E.; Canas, B.; Palacios, M. A.; Gomez-Gomez, M. M. Top-down mass spectrometric approach for the full characterization of insulin-cisplatin adducts. Anal. Chem. 2009, 81, 3507-3516. 26. Hartinger, C.; Tsybin, Y.; Fuchser, J.; Dyson, P. J. Characterization of platinum anticancer drug protein-binding sites using a top-down mass spectrometric approach. Inorg. Chem. 2008, 47, 17-19. 27. Mandal, R.; Li, X. Top-down characterization of proteins and drug-protein complexes using nanoelectrospray tandem mass spectrometry. Rapid Coummun. Mass Spectrom. 2006, 20, 48-52. 28. Kelleher, N. L.; Lin, H. Y.; Valaskovic, G. A.; Aaserud, D. J.; Fridriksson, E. K.; McLafferty, F. W. Top-down versus bottom-up protein characterization by tandem high resolution mass spectrometry. J. Am. Chem. Soc. 1999, 121, 806-812. 29. Zubarev, R. A.; Kruger, N. A.; Fridriksson, E. K.; Lewis, M. A.; Horn, D. M.; Carpenter, B. K.; McLafferty, F. M. Electron capture dissociation of gaseous multiply-charged proteins is favored at disulfide bonds and other sites of high hydrogen atom affinity. J. Am. Chem. Soc. 1999, 121, 2857-2862. 30. Zubarev, R. A.; Horn, D. M.; Fridriksson, E. K.; Keller, N. L.; Kruger, N. A.; Lewis, M. A.; Carpenter, B, K.; McLafferty, F. M. Electron capture dissociation for structural characterization of multiply charged protein cations. Anal. Chem. 2000, 72, 563-573. 31. Xie, Y.; Zhang, J.; Yin, S.; Loo, J. A. Top-dwon ESI-FT-ICR mass spectrometry localizes noncovalent protein-ligand binding sites. J. Am. Chem. Soc. 2006, 128, 14432-14433. 32. Breuker, K.; Jin, M.; Han, X.; Jiang, H.; McLafferty, F. M. Top-down identification and characterization of biomolecules by mass spectrometry. J. Am. Soc. Mass Spectrom. 2008, 19, 1045-1053. 33. Horn, D.; M.; Ge, Y.; McLafferty, F. W. Activated ion electron capture dissociation for mass spectral sequencing of larger (42 KDa) proteins. Anal. Chem. 2000, 72, 4778-4784. 34. Feketeova, L.; Ryzhov, V.; O’Hair, R. A. J. Comparison of collision- versus electron-induced dissociation of Pt(II) ternary complexes of histidine- and methionine-containing peptides. Rapid Commun. Mass Spectrom. 2009, 23, 3133-3143. 35. Li, H.; Zhao, Y.; Phillips, H. I. A.; Qi, Y.; Lin, T. Y.; Sadler, P. J.; O’Connor, P. B. Mass spectrometry evidence for cisplatin as a protein cross-linking reagent. Anal. Chem. 2011, 83, 5369-5376. 36. Timerbaev, A. R., Hartinger, C. G., Aleksenko, S. S., and Keppler, B. K. Interactions of Antitumor Metallodrugs with Serum Proteins: Advances in Characterization Using Modern Analytical Methodology. Chem. Rev. 2006, 106, 2224-2248. 37. Dhara, S.C. A rapid method for the synthesis of cis-[Pt(NH3)2Cl2]. Indian J. Chem. 1970, 8, 193-194. 38. Annibale, G.; Brandolisio, M.; Pitteri, B. Polyhedron. 1995, 14, 451-453. 39. Farrell, N.; Qu, Y. Chemistry of bis(platinum) complexes. Formation of trans derivatives from tetraamine complexes. Inorg. Chem. 1989, 18, 3416-3420. 40. Caravatti, P.; Allemann, A. The ‘infinity cell’: A new trapped-ion cell with radiofrequency covered trapping electrodes for Fourier transform ion cyclotron resonance mass spectrometry. Org. Mass Spectrom. 1991, 26, 514–518. 41. Tsybin, Y.O.; Quinn, J. P.; Tsybin, O. Y.; Hendrickson, C. L.; Marshall, A. G. Electron capture dissociation implementation progress in Fourier transform ion cyclotron resonance mass spectrometry. J. Am. Mass Spectrom. 2008, 19, 762-771. 42. Gorshkov, M. V.; Masselon, C. D.; Nokolaev, E. N.; Udseth, H. R.; Pasa-Tolic, L.; Smith, R. D. Considerations for electron capture dissociation efficiency in FTICR mass spectrometry. Int. J. Mass Spectrom. 2004, 234, 131-136. 43. Mormann, M.; Peter-katalinic, J. Improvement of electron capture efficiency by resonant excitation. Rapid Commun. Mass Spectrom. 2003, 17, 2208-2214. 44. Kasherman, Y.; Sturup, S.; Gibson, D. Trans labilization of am(m)ine ligands from platinum(II) complexes by cancer cell extracts. J. Biol. Chem. 2009, 14, 387-399. 45. Crider, S. E.; Holbrook, R. J.; Franz, K. J. Coordination of platinum therapeutic agents to metrich motif of human copper transport protein1. Metallomics. 2010, 2, 74-83. 46. Wu, Z.; Liu, W.; Liang, X.; Yang, X.; Wang, N.; Wang, X.; Sun, H.; Lu, Y.; Guo, Z. Reactivity of platinum-based antitumor drugs towards a Met- and His-rich 20mer peptide corresponding to the N-terminal domain of human copper transporter 1. J. Biol. Chem. 2009, 14, 1313-1323. 47. Oehlsen, M. E.; Qu, Y.; Farrell, N. Reaction of polynuclear platinum antitumor compounds with reduced glutathione studies by multinuclear (1H, 1H-15N gradient heteronuclear sing-quantum coherence, and 195Pt) NMR spectroscopy. Inorg. Chem. 2003, 42, 5498-5506. 48. Rodriguez, J.; Gupta, N.; Smith, R. D.; Pevzner, P. A. Does trypsin cut before proline? J. Proteome Research. 2007, 7, 300-305. 49. Carpenter, F. H. Treatment of trypsin with TPCK. Methods Enzymol. 1967, 11, 237. 50. Kleinnigenhuis, A. J.; Mihalca, R.; Heeren, R. M. A.; Heck, A. J. R. Atypical behavior in the electron capture induced dissociation of biologically relevant transition metal ion complexes of the peptide hormone oxytocin. Int. J. Mass Spectrom. 2006, 253, 217-224. 51. Liu, H.; Hakansson, K. Divalent metal ion-peptide interactions probed by electron capture dissociation of trications. J. Am. Mass Spectrom. 2006, 17, 1731-1741. 52. Turecek, F.; Jones, J. W.; Holm, A. I. S.; Panja, S.; Nielsen, S. B.; Hvelplund, P. Structures, 34. Feketeova, L.; Ryzhov, V.; O’Hair, R. A. J. Comparison of collision- versus electron-induced dissociation of Pt(II) ternary complexes of histidine- and methionine-containing peptides. Rapid Commun. Mass Spectrom. 2009, 23, 3133-3143. 35. Li, H.; Zhao, Y.; Phillips, H. I. A.; Qi, Y.; Lin, T. Y.; Sadler, P. J.; O’Connor, P. B. Mass spectrometry evidence for cisplatin as a protein cross-linking reagent. Anal. Chem. 2011, 83, 5369-5376. 36. Timerbaev, A. R., Hartinger, C. G., Aleksenko, S. S., and Keppler, B. K. Interactions of Antitumor Metallodrugs with Serum Proteins: Advances in Characterization Using Modern Analytical Methodology. Chem. Rev. 2006, 106, 2224-2248. 37. Dhara, S.C. A rapid method for the synthesis of cis-[Pt(NH3)2Cl2]. Indian J. Chem. 1970, 8, 193-194. 38. Annibale, G.; Brandolisio, M.; Pitteri, B. Polyhedron. 1995, 14, 451-453. 39. Farrell, N.; Qu, Y. Chemistry of bis(platinum) complexes. Formation of trans derivatives from tetraamine complexes. Inorg. Chem. 1989, 18, 3416-3420. 40. Caravatti, P.; Allemann, A. The ‘infinity cell’: A new trapped-ion cell with radiofrequency covered trapping electrodes for Fourier transform ion cyclotron resonance mass spectrometry. Org. Mass Spectrom. 1991, 26, 514–518. 41. Tsybin, Y.O.; Quinn, J. P.; Tsybin, O. Y.; Hendrickson, C. L.; Marshall, A. G. Electron capture dissociation implementation progress in Fourier transform ion cyclotron resonance mass spectrometry. J. Am. Mass Spectrom. 2008, 19, 762-771. 42. Gorshkov, M. V.; Masselon, C. D.; Nokolaev, E. N.; Udseth, H. R.; Pasa-Tolic, L.; Smith, R. D. Considerations for electron capture dissociation efficiency in FTICR mass spectrometry. Int. J. Mass Spectrom. 2004, 234, 131-136. 43. Mormann, M.; Peter-katalinic, J. Improvement of electron capture efficiency by resonant excitation. Rapid Commun. Mass Spectrom. 2003, 17, 2208-2214. 44. Kasherman, Y.; Sturup, S.; Gibson, D. Trans labilization of am(m)ine ligands from platinum(II) complexes by cancer cell extracts. J. Biol. Chem. 2009, 14, 387-399. 45. Crider, S. E.; Holbrook, R. J.; Franz, K. J. Coordination of platinum therapeutic agents to metrich motif of human copper transport protein1. Metallomics. 2010, 2, 74-83. 46. Wu, Z.; Liu, W.; Liang, X.; Yang, X.; Wang, N.; Wang, X.; Sun, H.; Lu, Y.; Guo, Z. Reactivity of platinum-based antitumor drugs towards a Met- and His-rich 20mer peptide corresponding to the N-terminal domain of human copper transporter 1. J. Biol. Chem. 2009, 14, 1313-1323. 47. Oehlsen, M. E.; Qu, Y.; Farrell, N. Reaction of polynuclear platinum antitumor compounds with reduced glutathione studies by multinuclear (1H, 1H-15N gradient heteronuclear sing-quantum coherence, and 195Pt) NMR spectroscopy. Inorg. Chem. 2003, 42, 5498-5506. 48. Rodriguez, J.; Gupta, N.; Smith, R. D.; Pevzner, P. A. Does trypsin cut before proline? J. Proteome Research. 2007, 7, 300-305. 49. Carpenter, F. H. Treatment of trypsin with TPCK. Methods Enzymol. 1967, 11, 237. 50. Kleinnigenhuis, A. J.; Mihalca, R.; Heeren, R. M. A.; Heck, A. J. R. Atypical behavior in the electron capture induced dissociation of biologically relevant transition metal ion complexes of the peptide hormone oxytocin. Int. J. Mass Spectrom. 2006, 253, 217-224. 51. Liu, H.; Hakansson, K. Divalent metal ion-peptide interactions probed by electron capture dissociation of trications. J. Am. Mass Spectrom. 2006, 17, 1731-1741. 52. Turecek, F.; Jones, J. W.; Holm, A. I. S.; Panja, S.; Nielsen, S. B.; Hvelplund, P. Structures,
URI:	http://wrap.warwick.ac.uk/id/eprint/40375

Request changes to a record

Actions (login required)

View Item