Department of Chemistry

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Sunil Saxena

Professor and Department Chair

Contact

711 CHVRN
Chevron Science Center, 219 Parkman Avenue

Pittsburgh, PA 15260
412-624-8680

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Research Overview

Analytical, Biophysical, and Physical Chemistry

We develop pulsed electron spin resonance methods and their application to otherwise inaccessible problems in biophysics and materials sciences. The coupling of electron spin angular momentum to its environment—as revealed by the ESR spectrum—provides rich information about the electronic, structural and dynamical properties of the molecule. We create methods that measure the precise distance between two units in a protein, in order to determine their folding patterns and conformational dynamics. These ESR Spectroscopic Rulers— based on multiple quantum coherences and double resonance experiments—are unique in that they resolve distances in the 1 - 7 nm lengthscale even on bulk amorphous materials. Much of this work is based on the use of first-principles theory to develop new experimental protocols and to analyze experimental results.

Our group continues to develop applications of these spectroscopic rulers that range from capturing the essence of structural changes - such as misfolding - in proteins, to measuring the atomic-level details of ion-permeation in a ligand gated ion-channel. We invite you to visit our group website and to contact us to explore the diversity of research projects currently underway in our group.

Projects include:

  • Pulsed ESR methods to measure distance constraints in systems containing paramagnetic metals
  • Measurement of structural and dynamical determinants of the protein-DNA interactions and functional dynamics in pentameric ligand gated ion-channels.
  • Application of the spectroscopic ruler to measure and predict global structures of nanostructured materials.
  • Role of metals in aggregation of Amyloid-b peptide.

Awards

  • Crano Memorial Lecture, ACS-Akron Section, 2014
  • Arts and Sciences Tina and David Bellet Teaching Excellence Award, 2012
  • NSF CAREER Award, 2004-2009

CV

Publications

“Increasing nitroxide lifetime in cells to enable in-cell protein structure and dynamics measurements by electron spin resonance spectroscopy,” K. Singewald, M. Lawless, S. Saxena J. Magn. Reson. 2019, 299, 21
“On the use of Q-band DEER to resolve relative orientations of two double-Histidine bound Cu2+-ions in a protein,” A.G. Jarvi, K. Ranguelova, S. Ghosh, R. Weber, S. Saxena J. Phys. Chem. B 2018, 122, 10669
“Copper oxidation dynamics in Cu2-xSe nanoparticles,” D.C. Kaseman, A.G. Jarvi, X.Y. Gan, S. Saxena, and J.E. Millstone Chem. Mater. 2018, 30, 7313
“Cu(II) EPR reveals two distinct binding sites and oligomerization of innate immune protein Calgranulin C,” S. Ghosh, V. Garcia, K. Singewald, S. Damo, and S. Saxena Appl. Magn. Reson. 2018, 49, 1299
“Rotamer modelling of Cu(II) spin labels based on the double-Histidine motif,” S. Ghosh, S. Saxena, G. Jeshke Appl. Magn. Reson. 2018, 49, 1281
“ESR shows that the C-terminus of Ligand Free Human Glutathione S-Transferase A1-1 exists in two conformations,” M. J. Lawless, J. R. Pettersson, G. S. Rule, F. Lanni, S. Saxena Biophys J. 2018, 114, 592
“On the use of Cu(II)-iminodiacetic acid complex in double-Histidine based distance measurements by pulsed electron spin resonance,” M. J. Lawless, S. Ghosh, T. F. Cunningham, A. Shimshi, and S. Saxena Phys. Chem. Chem. Phys. 2017, 19, 20959
“An analysis of nitroxide based distance measurements by pulsed ESR spectroscopy in cell-extract and in-cell,” M. J. Lawless, A. Shimshi, T. F. Cunningham, M. Kinde, P. Tang, and S. Saxena ChemPhysChem. 2017, 18, 1653
“Nucleotide-independent Cu(II)-based distance measurements in DNA by pulsed ESR,” M. J. Lawless, J. L. Sarver, S. Saxena Angew Chem 2017, 56, 2115
“Rotameric preferences of a protein spin label at edge-strand β-sheet sites,” T.F. Cunningham, S. Pornsuwan, W.S. Horne, S. Saxena Prot. Sci. 2016, 1049-1060
“Cu(II)-Zn(II) cross-modulation in Amyloid-b peptide binding: An X-ray Absorption Spectroscopy Study,” E. D. Santis, V. Minicozzi, S. Morante, O. Proux, G. Rossi, K. I. Silva, M. J. Lawless, S. Saxena, and F. Stellato J. Phys. Chem. B. 2015, 119, 15813
“Cu(II) as an ESR probe of protein structure and function,” Z. Yang, M. Ji, T. F. Cunningham, and S. Saxena Meth. Enzymol. 2015, 563, 459
“Conformational changes underlying pore opening and desensitization in the pentameric ligand gated ion channel ELIC,” M.N. Kinde, Q. Chen, M.J. Lawless, E. Seyoum, D.D. Mowrey, J. Xu, V. Bandarenko, T.S. Tillman, S. Saxena, Y. Xu, P. Tang Structure 2015, 23, 995
“The double histidine Cu(II)-binding motif: A highly rigid, site-specific spin probe for electron spin resonance distance measurements,” T.F. Cunningham, M.R. Putterman, A. Desai, W.S. Horne, S. Saxena Angew. Chem. Int. Ed. 2015, 6330-6334
“Origins of structural flexibilities in protein-based supramolecular polymers probed by DEER spectroscopy,” N. A. Tavenor, K. I. Silva, S. Saxena, W. S. Horne J. Phys. Chem. B. 2014, 118, 9881
“Insight into the Cu(II) binding site in a protein-DNA complex,” M. Ji, L. Tan, L. Jen-Jacobson, S. Saxena Mol. Phys. 2014, 112, 3173
“Paramagnetic metal ions in pulsed ESR distance distribution measurements,” M. Ji, S. Ruthstein, and S. Saxena Acc. of Chem. Res. 2014, 47, 688
“Sensitive Cu(II)-Cu(II) distance measurements in a protein-DNA complex by DQC-ESR,” S. Ruthstein, M. Ji, P. Mehta, L. Jen-Jacobson, and S. Saxena J. Phys. Chem. B 2013, 117, 6227
“Measuring Cu(II)-nitroxide distances using double electron-electron resonance and saturation recovery,” J. Sarver, K. I. Silva, and S. Saxena Appl. Magn. Reson. 2013, 44, 583