Scott A. Showalter

Scott A. Showalter

Main Content

  • Professor of Chemistry
  • Professor of Biochemistry and Molecular Biology
  • Graduate Program Chair
Office:
106 Chemistry Building
University Park, PA 16802
Email:
(814) 865-2318

Education:

  1. B.S. Cornell University, Ithaca 1999.
  2. Ph.D. Washington University School of Medicine, St. Louis 2004.
  3. Postdoc National High Magnetic Field Laboratory, Tallahassee 2005-2008.

Honors and Awards:

  1. Eastern Analytical Symposium New Faculty Award in NMR Spectroscopy, 2012
  2. NSF Career Award, 2010.
  3. NIH Ruth L. Kirschstein NRSA Postdoctoral Fellow 2005-2008.
  4. NSF Predoctoral Fellow 2000-2003.

Selected Publications:

Cook, EC, Sahu, D, Bastidas, M, Showalter, SA. (2019) "The Solution Ensemble of the C-Terminal Domain from the Transcription Factor Pdx1 Resembles an Excluded Volume Polymer." J. Phys. Chem. B., 123: 106-116.

Cook, EC, Featherston, ER, Showalter, SA, Cotruvo, JA. (2019) "Structural Basis for Rare Earth Element Recognition by Methylobacterium extorquens Lanmodulin." Biochemistry., 58: 120-125.

Cook, EC, Usher, GA, Showalter, SA. (2018) "The use of 13C Direct-Detect NMR to Characterize Flexible and Disordered Proteins." Methods Enzymol., 611: 81-100.

Burkholder, NT, Medellin, B, Irani, S, Matthews, W, Showalter, SA, Zhang, YJ. (2018) "Chemical Tools for Studying the Impact of cis/trans Prolyl Isomerization on RNA Polymerase II Phosphatase Activity and Specificity." Methods Enzymol., 607: 269-297.

Gibbs, EB, Laremore, TN, Usher, GA, Portz, B, Cook, EC, Showalter, SA. (2017) "Substrate Specificity of the Kinase P-TEFb Towards the RNA Polymerase II C-Terminal Domain." Biophys J., 113: 1909-1911.

Kranick, JC, Chadalavada, DM Sahu, D, Showalter, SA. (2017) "Engineering Double-Stranded RNA Binding Activity into the Drosha Double-Stranded RNA Binding Domain Results in a Loss of MicroRNA Processing Function." PLoS One., 12: e0182445. PMCID: PMC5549741.

Gibbs, EB, Cook, EC, Showalter, SA. (2017) "Application of NMR to Studies of Intrinsically Disordered Proteins." Arch Biochem Biophys.628: 57-70.

Gibbs, EB, Lu, F, Portz, B, Fisher, MJ, Medellin, BP, Laremore, TN, Zhang, YJ, Gilmour, DS, Showalter, SA. (2017) "Phosphorylation Induces Sequence-Specific Conformational Switches in the RNA Polymerase II C-Terminal Domain." Nat Commun., 8: 15233. PMCID: PMC5437310

Portz, B, Lu, F, Gibbs, EB, Mayfield, JE, Mehaffey, MR, Zhang, YJ, Brodbelt, JS, Showalter, SA, Gilmour, DS. (2017) "Structural Heterogeneity in the Intrinsically Disordered RNA Polymerase II C-terminal Domain." Nat Commun
8: 15231. PMCID: PMC5437306

Gibbs, E.B., & Showalter, S.A. (2016) "Quantification of Compactness and Local Order in the Ensemble of the Intrinsically Disordered Protein FCP1." J. Phys. Chem. B, 120, 8960-8969.

Acevedo, R., Evans, D., Penrod, K.A., & Showalter, S.A. (2016) "Binding by TRBP-dsRBD2 does not induce bending of double-stranded RNA." Biophys. J., 110, 2610-2617. PMCID: PMC4919420

Sahu, D., Bastidas, M., Lawrence, C.W., Noid, W.G., & Showalter, S.A. (2016) "Assessing COupled Protein Folding and Binding through Temperature-Dependent Isothermal Titration Calorimetry." Methods Enzymol., 567, 23-45. PubMed PMID: 26794349 PMCID: In Process

Yennawar, N.H., Fecko, J.A., Showalter, S.A., & Bevilacqua, P.C. (2016) "A High-Throughput Biological Calorimetry Core-- Steps to Startup, Run, and Maintain a Multi-User Facility." Methods Enzymol., 567, 435-460. PubMed PMID: 26794364 PMCID: In Process

Quarles, K.A., Chadalavada, D., & Showalter, S.A. (2015) "Deformability in the Cleavage Site of Primary MicroRNA is Not Sensed by the Double-Stranded RNA Binding Domains in the Microprocessor Component DGCR8." Proteins: Struct. Funct. Bioinf., 83, 1165-1179. PMCID: PMC4446130

Gibbs, E.B., & Showalter, S.A. (2015) “Quantitative Biophysical Characterization of Intrinsically Disordered Proteins.” Biochemistry, 54, 1314-1326.

Acevedo, R., Orench-Rivera, N., Quarles, K.A., & Showalter, S.A. (2015) “Helical Defects in MicroRNA Influence Protein Binding by TAR RNA Binding Protein.” PLoS One, 10, e0116749. PMCID: In Process

 

Information:

Biophysical Chemistry applied to solution NMR spectroscopy of partially disordered proteins. NMR studies of protein dynamics coupled with computational and theoretical studies of the coupling between nuclear spin relaxation and molecular motion. Emphasis is placed on biophysical studies of macromolecular interactions involving partially disordered proteins, for the purpose of understanding the functional implications of protein dynamics and disorder in protein mediated signaling and oncogenesis/ tumor suppression.

Dynamics and Disorder in Protein Ligand Interactions

Proteins are dynamic molecules and developing an intuitive understanding of the relationship between structure, dynamics, and function is a universally valuable goal. The primary research tools used by members of our laboratory are Nuclear Magnetic Resonance spectroscopy (NMR), molecular dynamics simulations (MD), and Isothermal Titration Calorimetry (ITC). Since our emphasis is on studying interactions involving disordered proteins and flexible agonists, the focus of the work is on the conformational dynamics of proteins and the contributions of these dynamics to protein-protein interactions. For flexible systems with disorder-order transitions coupled to the binding event, NMR spectroscopy remains the most powerful source of atomic level biophysical information available, with access to dynamics on the fast ps-ns timescale, as well as the biologically critical μs-ms timescale.  Shifting focus from backbone to side chain NMR dynamics further broadens the possibilities for understanding protein-protein interactions and non-folded systems.  Combined analysis of experimental NMR data and computational results provides a uniquely detailed picture of correlated dynamics. Rigorous protocols for cross validation of MD trajectories and theoretical calculations against diverse experimental NMR data are applied throughout the projects in our laboratory.

Research Interests:

Analytical

Biomolecular NMR spectroscopy, calorimetry studies of biomolecular systems.

Biological

Biophysical chemistry, macromolecular structure and dynamics by NMR

Physical

NMR spectroscopy and methods development, simulation of biological systems.

Departments:

Graduate Program