Prof. Sharon Ruthstein

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Magnetic Resonance, Structural Biology
Bldg. 211, Room 414. Laboratory Phone: 03-7384308, 03-5317682


Sharon Ruthstein gained her B.Sc in Chemical Engineering from the Technion, Haifa, Israel. Then she continued her graduate studies in the Chemistry Department at Weizmann Institute of Science, Rehovot, Israel. She achieved her PhD under the supervision of Prof. Daniella Goldfarb. After graduating from the Weizmann Institute in 2008, she became an EMBO Postdoctoral Fellow at the University of Pittsburgh, where she worked under the supervision of Prof. Sunil Saxena.

Prof. Ruthstein joined the Department of Chemistry at Bar-Ilan University in October 2011. Her research is aiming to exploit biological pathways in human and bacteria cells, which involve metal ions, using pulsed Electron Paramagnetic Resonance Spectroscopy (EPR).



Educational Background

2008-2011           EMBO Long-term Post-doctoral Fellow at the

                           University of  Pittsburgh, Department of Chemistry.

                           Advisor: Prof. Sunil Saxena.

2003-2008           Ph.D. in Chemistry, with Honors, Weizmann Institute of Science,

                           Israel.    Advisor: Prof. Daniella Goldfarb.

2000-2003           M.Sc in Chemistry, with Honors, Weizmann Institute of Science.

1996-2000           B.Sc in Chemical Engineering, (summa cum laude),

                           Technion,  Haifa, Israel.



2017 - present:  Associate Profeesor, Department of Chemistry, Bar-Ilan University.

2011- 2017:       Senior Lecturer, Department of Chemistry, Bar-Ilan University.


Awards and Fellowships

2017                ICS Young Scientist award

2017                ERC - STG

2015                Krill award (Wolf Foundation)

2008                EMBO Long-term Fellowship for post-doctoral studies.

2008                AAUW Post-doctoral fellowship – declined upon receiving the

                        EMBO  fellowship.

2007                Dean's Excellence Prize for Ph.D. – Weizmann Institute of Science.

2007               JEOL Student Prize 

2007               Auto Schwartz Prize – Weizmann Institute of Science.

2007               Wolf Foundation Fellowship for Excellent Ph.D. Students.

2004               Eshkol Scholarship for Ph.D. students, Jerusalem, Israel.

2003               Mention of Honor of the Knesset (The Israeli Parliament).

2003               Dean's Excellence Prize for M.Sc. – Weizmann Institute of Science,

1998               Sidney Goldstein Excellence Prize – Technion, Haifa, Israel.


Protein structure and function, structural biology, magnetic resonance, metalloproteins.


More than 30% of all proteins in the cell exploit one or more metals to perform their specific functions, and over 40% of all enzymes contain metals. Metals are commonly found as natural constituents of proteins; however, many metal ions can be toxic when free in biological fluids. Hence, the human bodies as well as microorganisms have evolved considerable regulatory machinery to acquire, utilize, traffic, detoxify, and otherwise manage the intracellular and extracellular concentrations and types of metal ions. Despite the high regulation of metal ions in the human body, diseases such as Menkes, Wilson, Alzheimer’s, Parkinson’s and Prion’s have been linked with metal binding to proteins.

Dr. Ruthstein’s lab will look into some of the significant and least understood biological processes that are related to metal ion transportation and intracellular distribution, as well as unwanted processes due to high metal concentration or protein mutations. The aims are:

(i)    To obtain structural information on intrinsically disordered N-terminal domain in metal transporters (such as Ctr1), in order to understand metal ion transportation to the cells.

(ii)   To understand the metal binding mechanism of metal sensors in bacterial cells, in order to shed light on the metal regulatory      machinery of the bacteria (CueR, CsoR).

(iii)  To explore the copper transport and distribution mechanisms in human cells (from Ctr1 through Atox1 to Atp7b), in order to get to the core of the copper homeostasis mechanism.

(iv)  To characterize the role of copper and mutations on the aggregation,folding of proteins, and protein-protein interactions in bacteria and human cells.


To comprehend such processes it is necessary to be sensitive to the structural changes that occur in the protein upon metal binding. The main biophysical tool that is used in the lab of Dr. Ruthstein’s lab is pulsed EPR spectroscopy. The power of EPR lies in the sensitivity to both atomic level changes and nanoscale fluctuations. EPR can characterize properties such as redox state and ligand geometry for different functional states of the protein. In addition, EPR can measure distances between paramagnetic probes up to 80 Å


  1. Otis, G.; Nassir, M.; Zutta, M.; Saady, A.; Ruthstein, S.; Mastai, Y.; Enantioselective crystallization of chiral inorganic crystals of ε-Zn(OH)2 with amino acids. Angew. Chem. Int. Ed. 2020, Accepted.
  2. Taub, T.; Ruthstein, S.; Cohen, H.; The Mechanism underlying the Emission of Gases during the Low-Temperature Oxidation of Bituminous and Lignite Coal Piles: The Involvement of Radicals.  ACS Omega. 2020. Accepted.
  3. Qasem, Z.; ZaccaK, M..; Gevorkyan-Airapetov, L.; Ruthstein, S.; An EPR study on the interaction between the Cu(I) metal binding domains of ATP7B and the Atox1 metallochaperone. Int. J. Mol. Sci. 2020, 21, 5539.
  4. Perkal. O; Qasem, Z.; Turgeman, M.; Schwartz, R.; Gevorkyan-Airapetov, L.; Pavlin, M.; Magistrato, A.; Major, D.; Ruthstein, S.; Cu(I) controls conformational states in the human metallochaperone Atox1: an EPR and multiscale simulation study. J. Phys. Chem. B. 2020, 124, 4399-4411.
  5. Susai, F.A; Sclar, H.; Maiti, S.; Burstein, L.; Perkal, O.; Grinblat, J.; Talianker, M.; Ruthstein, S.; Erk, C.; Hartmann, P.; Markovsky, B.; Aurbach, D.; Stabilized Behavior of LiNi0.85Mn0.05O2 Cathode Materials Induced by their treatment with SO2 . ACS Appl. Energ. Mater. 2020, 3, 3609-3618. 
  6. Levy, N.; Lori, O.; Gonen, S.; Mizrahi, M.; Ruthstein, S.; Elbaz, L.; The relationship of morphology and catalytic activity: A case study of iron corrole incorporated in high surface area carbon supports. Carbon 2020, 158, 238-243.
  7. Sameach, H.; Ruthstein, S.; EPR distance measurements as a tool to chracterize protein-DNA complexes. Isr. J. Chem. 2019, 59, 980-989.
  8. Meir, A.; epechkin-Zilbermintz, V.; Kahremany, S.; Schwerdtfeger, F.; Gevorkyan-Airapetov, L.; Munder, A.; Viskind, O.; Gruzman, A.; Ruthstein, S.; Inhibiting the copper efflux system in microbes as a novel approach for developing antibiotics. BioRxiv, 2019.
  9. Pavlin, M.; Qasem, Z.; Sameah, H.; Gevorkyan-Airapetov, L.; Ritacco, I.; Ruthstein, S.; Magistrato, A.;  Unraveling the impact of Cysteine-to-Serine mutations on the structural and functional properties of Cu(I)-binding proteins. Int. J. Mol. Sci. 2019, 20, 3462.
  10. Walke, G.; Ruthstein, S.; Does the ATSM-Cu(II) biomarker integrate into the human cellular copper cycle? ACS Omega. 2019. 10.1021/acsomega.9b01748
  11. Meir, A.; Walke, G.; Schwerdtfeger, F.; Gevorkyan-Airapetov, L.; Ruthstein, S.; Exploring the role of the various methionine residues in the Escherichia coli CusB adapter protein. BioRxiv. 2019. Plos One, 2019.
  12. Qasem, Z.; Pavlin, M.; Ritacco, I.; Gevorkyan-Airapetov, L.; Magistrato, A.;  Ruthstein, S.; The pivotal role of MBD4-ATP7B in the human Cu(I) excretion path as revealed by EPR experiments and all-atom simulations. Metallomics. 2019, 11, 1288-1297.
  13. Magistrato, A.;  Qasem, Z.; Pavlin, M.; Ruthstein, S.; Copper trafficking in eukaryotic systems: Current knowledge from experimental and computational efforts. Curr. Opin. Struct. Biology. 2019, 58, Accepted.
  14. Sameach, H.; Ghosh, S.; Gevorkyan-Airapetov, L.; Saxena, S.; Ruthstein, S.; EPR Spectroscopy detects various active state conformation of the transcriptional regulator CueR. Angew. Chem. Int. Ed. 2019, 58, 3053-3056. (selected as cover)
  15. Munder, A.; Moskovitz, Y.; Meir, A.; Levy, L.; Kahremany, S.;  Kolitz-Domb, M.; Cohen, G.; Shtriker, E.; Viskind, O.; Lellouche, J.-P.; Senderowitz, H.; Chessler, S.;   Korshin, E.; Ruthstein, S.; Gruzman, A.; Covered by Neuroligin-2-derived peptide polyamidoamine-based (PAMAM) dendrimers enhances panceratic b-cells'proliferation and function.  Med. Chem. Comm. 2019, 10, 280-293.
  16. Qasim, A.; Sher, I.; Hirschhorn, O.; Shaked, H.; Qasem, Z.; Ruthstein, S.; Chill, J. ; A KcsA cytoplasmic pH-gate investigated in lipoprotein nanodiscs.  ChemBioChem. 2019, 20, 813-821.
  17. Snitkoff, R.Z.; Levy, N.; Ozery, I.; Ruthstein, S.; Elbaz, L. ; Imidazole decorated reduced graphene oxide: a biomimetic ligand for selective oxygen reduction electrocatalysis with metalloporphyrins. Carbon. 2019, 143, 223-229.
  18. Taub, T.; Ruthstein, S.; Cohen, H.; The involvement of carbon-centered radicals in the aging process of coals under atmospheric conditions: an EPR study. PCCP, 2018. in press.
  19. Kahremany, S.; Zhenin, M.; Shenberger, Y.; Maimoun, D.; Colotti, G.; Arad, M.; Shainberg, A.; Sendrowitz, H.; Ruthstein, S.; Gruzman, A.; Peptide-based development of PKA activators. New J. Chem. 2018, in press.
  20. Shenberger, Y.; Marciano, O.; Gottlieb, H.; Ruthstein, S.; Insights into the N-terminal Cu(II) and Cu(I) binding sites of the human copper transporter Ctr1. J. Coord. Chem. 2018, 71, 1985-2002.
  21. Levy, A.; Turgeman, M.; Gevorkyan-Aiapetov, L.; Ruthstein, S.; The structural flexibility of the human copper chaperone Atox1: Insights from combined pulsed EPR studies and computations. Protein Sci. 2017, 26, 1609-1618.
  22. Meir, A.; Abdelhai, A.; Moskovitz, Y.; Ruthstein, S.; EPR spectroscopy targets conformational and topological changes in the E.coli membrane fusion CusB dimer upon Cu(I) binding. Biophys. J. 2017, 112, 2494-2502.
  23. Sameach, H.; Narunsky, A.; Azoulay-Ginsburg, S.; Gevorkyan-Aiapetov, L.; Zehavi, Y.; Moskovitz, Y.; Juven-Gershon, T.; Ben-Tal, N.; Ruthstein, S.; Structural and dynamics characterization of the MerR family metalloregulator CueR in its repression and activation states. Structure. 2017, 25, 988-996.
  24. Levy, A.; Nissim, M.; Mendelman, N.; Chill, J.; Ruthstein, S.; Ctr1 intracellular loop is involved in the copper transfer mechanism to the Atox1 metallochaperone. J. Phys. Chem. B. 2016, 120, 12334-12345.
  25. Marciano, O.; Gonen, S; Levy, N.; Yemini, R; Nessim, G.; Ruthstein, S.; Elbaz, L.; Modulation of oxygen content in graphene surfaces using temperature programmed reductive annealing: electron paramagnetic resonance (EPR) and electrochemical study. Langmuir, 2016, 32, 11672-11680.
  26. Zer-Aviv, P.; Shubely, M.; Moskovitz, Y.; Viskind, O.; Albeck,  A.; Vertommen,  D.; Ruthstein, S.; Shokhen, M.; and  Gruzman, A. . A new oxopiperazin-based peptidomimetic molecule inhibits prostatic acid phosphatase secretion and induces prostate cancer cells apoptosis. Chemistry Select, 2016, 1, 4658-4667.
  27. Fleker, O.; Borenstein, A.; Lavi, R.; Ruthstein, S.; Aurbach D.; Preparation and properties of metal organic framework/activated carbon composite materials. Langmuir. 2016, 32, 4935-4944.
  28. Shilina, Y.; Ziv, B.; Meir, A.; Banerjee, A.; Ruthstein, S.; Luski, S.; Aurbach, D.; Halalay, I.C.; Combined EPR and AAS/ICP analysis as diagnostics for soluble maganese species from Mn-based positive electrode materials in Li-ion cells. Anal. Chem. 2016, 88, 4440-4447.
  29. Marciano, O.; Moskovitz, Y.; Hamza, I.; Ruthstein, S.; Histdine residues are important for preserving the structure and heme binding to the c.elegans HRG-3 heme trafficking protein. J. Biol. Inorg. Chem. 2015, 20, 1253-1261.
  30. Weintraub, S.; Moskovitz, Y.; Fleker, O.; Levy, A.; Meir, A.; Ruthstein, S.; Benisvy, L.; Gruzman, A.; SOD mimetic activity and antiproliferative properties of a novel tetra nuclear copper(II) complex. J. Biol. Inorg. Chem. 2015, 20, 1287-1298.
  31. Dalalyon, A.; Qi, M.; Ruthstein, S.; Vega, S.; Godt, A.; Feintuch, A.; Goldfarb, D.; Gd(III)-Gd(III) EPR distance measurments - the range of accessible distances and the impact of zero field splitting. PCCP, 2015, 17, 18464-18476.
  32. Meir, A.; Natan, A.; Moskovitz, Y.; Ruthstein, S.; EPR spectroscopy identifies Met and Lys rediues that are essential for the interaction between CusB N-terminal domain and the metallochaperone CusF. Metallomics, 2015, 7, 1163-1172.
  33. Shenberger, Y.; Shimshi, A.; Ruthstein, S.; EPR spectroscopy shows that the blood carrier protein, human serum albumin, closley interacts with the N-terminal domain of the copper transporter, CTR1. J. Phys. Chem. B. 2015, 119, 4824-4830.
  34. Shenberger, Y.; Gottlieb, H.; Ruthstein, S.; EPR and NMR spectroscopies provide input on the coordination of Cu(I) and Ag(I) to a disordered methionine segment. J. Biol. Inorg. Chem. 2015, 20, 719-727. 
  35. Ruthstein, S.; Ji, M.; Shin, B.K.; Saxena, S.; A simple double quantum coherence ESR sequence that minimizes nuclear modulation in Cu(II)-ion based distance measurments. J. Magn. Reson. 2015, 257, 45-50.
  36. Munder, A.; Moskovitz, Y.; Rediko, B.; Levy, A.; Ruthstein, S.; Gellerman, G.; Gruzman, A.; Antiproliferative Effects of Novel Aminoacridine-Based Compounds. Med. Chem. 2015. 11, 373-382.
  37. Levy, A.; Yarmiayev, V.; Moskovitz, Y.; Ruthstein, S.; Probing the Structural Flexibility of the Human Copper Metallochaperone Atox1 Dimer and its Interaction with the CTR1 C-Terminal Domain. J. Phys. Chem. B. 2014, 118, 5832-5842.
  38. Green, U.; Keinan-Adamsky, K.; Attia, S.; Aizenshtat, Z.; Goobes, G.; Ruthstein, S.; Cohen, H.; Elucidating the role of stable carbon radicals in the low temperature oxidation of coals by coupled EPR-NMR spectroscopy - a method to characterize surfaces of porous carbon radicals. PCCP. 2014, 16, 9364-9370.
  39. Green, U.; Shenberger, Y.; Aizenshtat, Z.; Cohen, H. Ruthstein, S.; Exploring the radical nature of a carbon surface by Electron Paramagnetic resonance and a calibrated gas flow. JoVE, 2014, .86, doi:10.3791/51548.
  40. Ji, M.; Ruthstein, S.; Saxena, S.; Paramagnetic metal ions in Pulsed ESR distance measurements. Acc. Chem. Res. 2014, 47, 688-695.
  41. Rubinovich, L.; Ruthstein, S.; Weiss, D.; The Arabidopsis cysteine-rich GASA5 is a redox-active metalloprotein that suppresses gibberellin responses. Mol. Plant. 2014, 7(1), 244-247.
  42. Shenberger, Y.; Yarmiayev, V.; Ruthstein, S.; Exploring the interaction between the human copper transporter, CTR1, c-terminal domain and a methionine motif, in the presence of Cu(I) and Ag(I) ions, using EPR spectrosopy. Mol. Phys. 2013, 111, 2980-2991.
  43. Ruthstein,S.; Ji, M.; Mehta, P.; Jen-Jacobson, L.; Saxena, S.K.; Sensitive Cu2+-Cu2+ distance measurements in a protein-DNA complex by Double-Quantum Coherence ESR. J. Phys. Chem. B. 2013, 117, 6227-6230.
  44. Green, U.; Aizenshtat, Z.; Ruthstein, S.; Cohen, H.; Reducing the spin-spin interaction of stable carbon radicals. PCCP, 2013, 15, 6182-6184.
  45. Green, U.; Aizenshtat, Z.; Ruthstein, S.; Cohen, H.; Stable radicals formation in coals undergoing weathering: effect of coal rank. PCCP, 2012, 14, 13046-13052.
  46. Ruthstein S.; Stone, K.M.; Cunningham, T.F.; Ming, J.; Cascio, M.; Saxena, S.; Pulsed Electron spin Resonance resolves the coordination site of Cu(II) ions in glycine receptor. Biophysical Journal, 2010, 99(8), 2497-2506.
  47. Omer L.; Ruthstein S.; Goldfarb, D.; Talmon, Y.; High resolution cryogenic-electron microscopy reveals details of a hexagonal-to-bicontinuous cubic phase transition in mesoporous silica synthesis, J. Am. Chem. Soc., 2009, 131, 12466-12473.
  48. Ruthstein, S.; Raitsimring, A.M.; Bitton, R.; Frydman, V.; Godt, A.; Goldfarb, D.; Distribution of guest molecules in Pluronic micelles studied by double electron electron spin resonance and small angle X-ray scattering. PCCP, 2009, 11, 148-160.
  49. Ruthstein, S.; Goldfarb, D.; An EPR tool box for exploring the formation and properties of ordered template mesoporous materials. Electron Paramagnetic Resonance, 2008, 21, 184-215.
  50. Ruthstein, S.; Goldfarb, D.; Evolution of solution structures during the formation of cubic mesoporous material, KIT-6, determined by double electron electron resonance. J. Phys. Chem. C, 2008, 112, 7102-7109.
  51. Ruthstein, S.; Schmidt, J.; Kesselman, E.; Popovits-Biro, R.; Frydman, V.; Omer, L.; Talmon, Y.; Goldfarb, D.; Molecular level Processes and nanostructure evolution during the formation of the cubic mesoporous material KIT-6. Chem. Mater. 2008, 20, 2779-2792.
  52. Ruthstein, S.; Schmidt, J.; Kesselman, E.; Talmon, Y.; Goldfarb, D.; Resolving Intermediate Solution Structure During the Formation of Mesoporous SBA-15.  J. Am. Chem. Soc. 2006, 128, 3366-3374.
  53. Ruthstein, S.; Potapov, A.; Raitsimring, A.M.; Goldfarb, D.; Double Electron Electron Resonance as a Method for Characterization of Micelles. J. Phys. Chem .B. 2005, 109, 22843-22851.
  54. Ruthstein, S.; Artzi, R.; Goldfarb, D.; Naaman, R.; EPR Studies on the Organization of Self-assembled organic monolayers adsorbed on GaAs. PCCP, 2005, 7, 524-529.
  55. Ruthstein, S.; Frydman, V.; Goldfarb, D.; Study of the Initial Formation Stages of the Mesoporous Materials SBA-15 Using Spin-Labeled Block Co-polymer Templates. J. Phys. Chem. B. 2004, 108, 9016-9022.
  56. Ruthstein, S.; Frydman, V.; Kababya, S.; Landau, M.; Goldfarb, D; Study of the Formation of the Mesoporous Material SBA-15 by EPR Spectroscopy. J. Phys. Chem. B. 2003, 107, 1739-1748.



Physical Chemistry II

Introduction to Electron Paramagnetic Resonance Spectroscopy

Physical Chemistry Lab 






Research Group

Group members:

Dr. Lada Gevorkya Airapetov (Research assistant)
Dr. Yulia Shenberger (Research assistant)
Dr. Gulshan Walke (Post-doctoral fellow)
Dr. Lukas Hofmann (Post-doctoral fellow)
Ms. Zena Bishara (PhD student)
Ms. Shelly Meiron (PhD student)
Ms. Yasmin Algeberia (MSc student)
Ms. Melanie Hirsch (MSc student)
Ms. Hadeel Kashou (MSc student)
Mr. Idan Yacoboub (MSc Student)


Former group members
Mrs. Meital Turgeman
Mr. Ahmad Abdelhai 
Mr. Michael Zaccak
Mrs. Renana Schwartz
Dr. Ariel Levy
Ms. Yulia Glick
Mrs. Valeria Yarmiayev
Ms. Salome Azoulay
Ms. Adi Natan
Dr. Yoni Moskovitz
Dr. Aviv Meir
Dr. Hila Sameach
Dr. Ortal Perkal