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Scholarly Interest Report
Edward P. Nikonowicz
Professor of Biochemistry and Cell Biology
  • B.S. Biology (1985) St. Louis University, St. Louis, Missouri
  • Ph.D. Chemistry (1990) Purdue University, West Lafayette, Indiana
Primary Department
   Department of BioSciences
Department Affiliations
  • Institute of Biosciences and Bioengineering
  • Keck Center for Quantitative Biomedical Sciences
    Research Areas
     RNA-Protein biochemistry, structure, function Small molecule-RNA interactions

    Research Statement 2016


    Our laboratory focuses on understanding structure-function relationships in nucleic acid systems. In addition to NMR spectroscopy, we use biochemical and other biophysical methods (SAXS, single molecule FRET, x-ray crystallography) to investigate the kinetic, motional, and structural properties of the component molecules.

     The data obtained from these methods complement physiological and genetic information. One focus of the lab centers on post-transcriptional modification of tRNA and the contributions of modifications to tRNA-mediated gene expression through T-box riboswitch mechanism. The bases of tRNA molecules are modified in all cells. Modification, especially within the anti-codon loop, has been linked to translational fidelity and efficiency and regulation in prokaryotes. We are examining structural properties and the kinetic parameters of T-box riboswitch-tRNA binding to develop mechanistic models. Modifications throught tRNA affect the molecule's structure and stability. We are elucidating the roles of various tRNA modifications on the efficiency of riboswitch function in the cell and on the kintics of riboswitch-tRNA binding. These studies also will extend our understanding of the contributions of tRNA modification to Gram positive bacterial cell physiology and fitness. 

     Non-coding RNAs (nc-RNA), including rRNAs, riboswitches, and pre-microRNAs, often have an architecture containing a variety of non-canonical features that are key for the molecules' structures and function, therefore, the detailed structure provides an important backdrop to interpret functional and mechanistic studies. Small molecules that bind to specific RNA structure motifs can become powerful tools for probing RNA conformation and folding and to facilitate studies of specific RNA activities in vitro and in vivo. We are using NMR spectroscopy to define the breadth of conformational space accessed by a set of frequently occurring non-canonical RNA motifs. A computational workflow, that integrates the NMR-defined structure information and in silico screening of virtual chemical libraries is being used to identify chemical compounds that selectively bind to these non-canonical motifs. The interactions of these small molecules with RNAs are being characterized using biophysical and high-resolution structure methods including NMR spectroscopy and X-ray crystallography. 

     Another system involves the interaction of primary ribosomal proteins with their RNA targets and provides the opportunity to not only explore the specificity of RNA-ligand interactions, but also to examine the co-folding of protein and RNA molecules and maturation of the 30S (prokaryotic) and 40S (eukaryotic) ribosomal subunit. The primary RNA binding site for the S8 protein folds around a Mg2+ ion to form an unusual tertiary structure made up of non-Watson-Crick interactions. Once bound, S8 stabilizes the interaction of other ribosomal proteins with the 16S rRNA and guides folding of the RNP subdomains to yield the mature 30S particle. 

    Teaching Areas
     Biophysics, Structural Biology
    Selected Publications
     Refereed articles

    Chang, A.T., Tran, M. and Nikonowicz, E.P. "Structure and Dynamics of the Tetra-A Loop and (A-A)-U Sequence Motif within the Coliphage GA Replicase RNA Operator", Biochemistry, submitted.


    Fang, X., Michnicka, M., Wang, Y-X. and Nikonowicz, E.P. "Capture and release of tRNA by the T-loop receptor in the function of the T-box riboswitch", Nucleic Acids Res., revision submitted.


    Monroig-Bosque, P.C., Shah, M., Ivan, C., Nouraee, N., Chen, L., Jung, E-J., Lehrer, M., Monroig-Bosque, M.M., Ling, H., Irimie, A., Rivera, C., Dumitru, C.D., Berindan-Neagoe, I., Zhang, S., Nikonowicz, E.P., Calin, G.A. Small molecule inhibitor targets oncomiR-10b through a direct interaction, Scientific Reports, In revision.


    Suddala, K.C., Michnicka, M., Nikonowicz, E.P., and Walter, N.G. "Kinetic mechanism of amino acid sensing by a T-box riboswitch", Nature Chem. Biol., in preparation.


    Davlieva, M., Donarski, J., Wang, J., Shamoo, Y. and Nikonowicz, E. P. "Structure analysis of an RNA aptamer against ribosomal protein S8 from Bacillus anthracis." Nucleic Acids Research, 42 (2014) : 10795-808.Submitted


    Donarski, J., Moran, S., Wang, J., and Nikonowicz, E.P. "Structure of Helix 35 Stem-loop from Escherichia coli 23S rRNA and Binding of Methyl Transferase RlmA." in preparationIn Progress


    Sripakdeevong P, Cevec M, Chang AT, Erat MC, Ziegeler M, Zhao Q, Fox GE, Gao X, Kennedy SD, Kierzek R, Nikonowicz EP, Schwalbe H, Sigel RK, Turner DH, Das R "Structure determination of noncanonical RNA motifs guided by šH NMR chemical shifts." Nat Methods., 11(4) (2014) : 413-6.

    doi: 10.1038/nmeth.2876

    Suddala, K.C., Michnicka, M., *Nikonowicz, E.P. and *Walter, N.G. "Single Molecule Fluorescence Structure and Kinetics Analysis of the tRNA-T box Riboswitch Complex." in preparationIn Progress


    Thapar R, Denmon AP, Nikonowicz EP. "Recognition modes of RNA tetraloops and tetraloop-like motifs by RNA-binding proteins." Wiley Interdiscip Rev RNA. , 5 (2014) : 49-67.


    Chang AT, Nikonowicz EP. "Solution NMR determination of hydrogen bonding and base pairing between the glyQS T box riboswitch Specifier domain and the anticodon loop of tRNA(Gly)." FEBS Lett., 587(21) (2013) : 3495-9.


    Wang, J., Chang, A.T. and Nikonowicz, E.P. "The apical and AG loops in stem I of the T-box riboswitch fold to cradle the elbow of bound tRNA." in revisionSubmitted


    Chang, A.T. and Nikonowicz, E.P. "Solution nuclear magnetic resonance analyses of the anticodon arms of proteinogenic and nonproteinogenic tRNA(Gly)." Biochemistry, 51 (2012) : 3662-74.


    Denmon, A.P. Wang, J. and Nikonowicz, E.P. "Conformation effects on the anticodon stem-loop of tRNATyr from Bacillus subtilis." J. Mol. Biol., 412 (2011) : 285-303.


    Hammerstrom, T., Roh, J.H., Nikonowicz, E.P. and Koehler, T.M. "Bacillus anthracis Virulence Regulator AtxA: Oligomeric state, function, and CO2-signaling." Mol. Microbiol, 82 (2011) : 634-647.


    Wang, J., and Nikonowicz, E.P. "Solution structure of the K-turn/Specifier Loop domains from the Bacillus subtilis tyrS T box leader RNA." J. Mol. Biol., 408 (2011) : 99-117.


    Wang, J., Henkin, T.M. and Nikonowicz, E.P. "NMR Structure and Dynamics of the Specifier Domain from the Bacillus subtilis tyrS T box leader RNA." Nucleic Acids Res., 38 (2010) : 3388-3398.


    Xia, Y., Moran, S., Nikonowicz, E.P., and Gao, X. "Z-Restored spin echo 13C 1D spectrum of straight baseline free of Hump, Dip and Roll." Mag. Reson. Chem., 46 (2008) : 432-435.


    Xia, Y., Moran, S., Nikonowicz, E.P., and Gao, X. "“Z-Restored spin echo 13C 1D spectrum of straight baseline free of Hump, Dip and Roll." Mag. Reson. Chemistry (2007) In Press


    Tworowska, I. and Nikonowicz, E.P. "Base pairing within the ψ32, ψ39-modified anticodon arm of Escherichia coli tRNAPhe." Journal of the American Chemical Society, 128 (2007) : 15571-15572.


    Boisbouvier, J., Bryce, D., O'Neil-Cabello, E., Nikonowicz, E.P., and Bax, A. "Resolution-optimized NMR measurement of 1DCH, 1DCC, and 2DCH residual dipolar couplings in nucleic acid bases." J. Biomol. NMR, 30 (2005) : 287-301.


    Cabello-Villegas, J., and Nikonowicz, E.P. "Solution structure of psi32-modified anticodon stem-loop from Escherichia coli rTNAPhe." Nucleic Acids Res., 33 (2005) : 6961-6971.


    Jaroniec, C.P., Boisbouvier, J., Tworowska, I., Nikonowicz, E.P., and Bax. A. "Accurate measurement of 15N-13C residual dipolar couplings in nucleic acids." J. Biomol. NMR, 31 (2005) : 231-241.


    Cabello-Villegas, J., Tworowska, I., and Nikonowicz, E.P. "Metal ion stabilization of the U-turn of the A37 N6-dimethylallyl-modified anticodon stem-loop of Escherichia coli tRNAPhe." Biochemistry, 43 (2004) : 55-66.


    O'Neil-Cabello, E., Bryce, D.L., Nikonowicz, E.P., and Bax, A. "Local order in RNA from simultaneous measurement of dipolar couplings." J. Amer. Chem. Soc., 126 (2004) : 66-67.


    O'Neil-Cabello, E., Wu, Z., Bryce, D., Nikonowicz, E.P., and Bax, A. "Enhanced spectral resolution in RNA HCP spectra for measurement of 3JC2'P and 3JC4'P couplings and 31P chemical shift changes upon weak alignment." J. Biomol. NMR, 30 (2004) : 61-70.


    Tworowska, I., and Nikonowicz, E.P. "Site specific enzymatic incorporation of pseudouridine into RNA oligonucleotides." J. Amer. Chem. Soc. (2004) Submitted


    Cabello-Villegas, J., Tworowska, I., and Nikonowicz, E.P. "Cobalt hexamine but not Mg2+ stabilizes the U-turn of the A37 N6-dimethylallyl modified anticodon stem-loop of Escherichia coli tRNAPhe." Biochemistry (2003) In Press


    Miclet,, E., OżNeil-Cabello, E., Nikonowicz, E.P., Live, D., and Bax, A. "1H-1H dipolar couplings provide a unique probe of RNA backbone structure." Journal of the American Chemical Society (2003) In Press


    Cabello-Vellegas, J., Winkler, M.E., and Nikonowicz, E.P. "Solution conformations of unmodified and A37 N6-dimethylallyl modified anticodon stem-loops of Escherichia coli tRNAPhe." J. Mol. Biol., 319 (2002) : 1015-1034.


    DeJong, E., Marzluff, W.F., and Nikonowicz, E.P. "NMR structure and dynamics of the RNA binding site for the histone mRNA stem-loop binding protein." RNA, 8 (2002) : 83-96.


    Cabello-Vellegas, J., and Nikonowicz, E.P. "Detecting duplex and hairpin conformations of short oligonucleotides using chemical shifts." Nucleic Acids. Res., 28 (2000) : 74-77.


    Smith, J.S., and Nikonowicz, E.P. "Phosphorothioate substitution can substantially alter RNA conformation." Biochemistry, 39 (2000) : 5642-5652.


    Nikonowicz, E.P., and Smith, J.S. "NMR Spectroscopic investigations of phosphorothioate containing RNAs." Phosphorus, Sulfur, & Silicon, 146 (1999) : 305-308.


    Kalurachchi, K., and Nikonowicz, E.P. "NMR Structure Determination of the Binding Site for Ribosomal Protein S8 in Escherichia coli 16S rRNA." J. Mol. Biol., 280 (1998) : 639-654.


    Nikonowicz, E.P., Michnicka, M., and DeJong, E. "Improved NOE-based Sequential Correlation of Base and 1' Proton Resonances in Labeled Nucleic Acids." J. Amer. Chem. Soc., 120 (1998) : 3813-3814.


    Smith, J.S., and Nikonowicz, E.P. "NMR Structure and Dynamics of an RNA Motif Common to the Spliceosome Branchpoint Helix and the RNA Binding Site for Phage GA Coat Protein." Biochemistry, 37 (1998) : 13486-13498.

     Book chapters

    Nikonowicz, E.P. "Preparation of 2H-labeled RNA oligonucleotides and their use in NMR studies." Methods Enzymol., 338 (2001) : 320-341.


    Zimmermann, R.A., Alimov, I., Uma, K., Wu, H., Wower, I., Nikonowicz, E.P., Drygin, D., Dong, P., and Jiang, L. "How ribosomal proteins and rRNA recognize one another." in The Ribosome: Structure, Function, Antibiotics, and Cellular Interactions, (2000) : 93-104.

     Invited Talks

    “Recognition of Small RNA Motifs” 72nd Southwest Region Meeting of The American Chemical Society, Galveston, Texas, November 10-13, 2016.


    "Studies of the T-box Riboswitch:tRNA Transcription Regulatory Complex." 69th Southwest Region Meeting of The American Chemical Society, Waco, Texas. (November 16-19, 2013)


    "The T box Riboswitch and It’s RNA Ligands: Structure and Function." St. Louis University, St. Louis, MO, (May 4, 2012)


    "Structural Studies of the tyrS T-box Transcriptional Regulatory Element and the Anticodon Arm of tRNATyr." 22nd tRNA Workshop, Uppsala University, Uppsala, Sweden. (November 1-6, 2007)


    Speaker.  "RNA Base Modification:Getting RNA into Shape?." Department of Biology, Indiana University. (March 19, 2006)


    Speaker.  "Targeting Ribosome Assembly: RNA Aptamer Selection and Structural Analysis." 62nd Southwest Regional Meeting of The American Chemical Society, Houston, Texas. (October 19-22, 2006) With James Donarski, Linda Geng, Yousif Shamoo


    "Applications of High Resolution NMR to Studies of RNA." Annual Symposium of the Institute of Biosciences and Biotechnology, Houston, Texas. (July 7, 2005)


    "Base Modification: Getting RNA into Shape." Combined Biology & Chemistry Colloqium, Louisiana State University, Baton Rouge, Lousiana. (November 2, 2005)


    "Base Modification: Getting RNA into Shape." Pacific Northwest National Laboratory, Richland, Washington. (October 27, 2005)


    "Crystal Structure of Bacillus anthracis r-Protein S8 and RNA Aptamer Selection." 3rd Annual Meeting of Region VI RCE, UT San Antonio, San Antonio, Texas. (October 25, 2005)


    "Targeting Ribosome Assembly in Bacillus anthracis." 2bd Batuibak Neetubg if B/U/aUD RCE in Bioterrorism and Emerging Infectious Diseases, UTMB, Galveston, Texas. (March 14, 2005)


    "Structural effects of sequential base modifications in E. coli ACSLPhe." University of Utah, Salt Lake City, Utah. (April 27-28)


    Presenter.  "Base Modification and RNA Structure." First Houston High Field NMR Symposium, Houston, TX. (5/16/03) With None


    speaker.  "Thioaptamer-guided Targeting of Ribosome Assembly in Bacillus anthracis." 1st Annual Meeting of Region VI RCE, UTMB, Galveston. (12/02/03)


    Speaker.  "Alteration of RNA Structure through Base and Backbone Modification: A Solution NMR Study." Biochemistry Department, University of Texas Medical School, Houston, TX. (January 14, 2002)


    Speaker.  "Solution NMR Investigation of Base Modification in RNA." DIRAG/GCC MR Symposium, Galveston, TX. (March 6, 2002)


    Lecturer in UT Health/MD Anderson Graduate School of Biomedical Sciences course “Principles of Therapeutics”. Lecture topic “DNA and RNA Aptamers: Therapeutics, Diagnostics, and Research Tools” March 4, 2016.


    Session Chair.  "Session Chair." 7th Annual Structural Biology Symposium at UTMB, Galveston, TX. (May 15-17, 2002)


    "Context Sensitivity of a Common RNA Secondary Structure Motif." University of Texas San Antonio, San Antonio, Texas. (May 3-4, 2001)


    "Lecturer." University of Science & Technology, Hefei, P.R.C.. (September 10, 2000)


    "Lecturer." Peking University, Peking, P.R.C.. (September 9, 2000)


    "Individual And Cummulative Effects Of Sequential Base Modifications In E. coli ACSL-phe." Gordon Research Conference (Nucleic Acids), Salve Regina University. (June 3-8, 2007)


    "NMR Studies of the H/ACA Box Guide RNA from Euglena." 12th Annual RNA Society Meeting, Madison, Wisconsin. (June 1-5, 2007)


    Postdoctoral advisor.  "tRNA(Phe) Modifications Reveal Their Secret." IBB Symposium, Rice University, Houston, Texas. With I. Tworowska


    presenter.  "Individual and Cumulative Effects of Sequential Base Modifications in E. coli ACSLPHE." Annual Meeting of the RNA Society, University of Washington. (June 20-25, 2006) With Tworowska, I.


    co-author.  "Structural Studies of the H/ACA Box Guide RNA from Euglena gracilis." Annual Meeting of the Keck Center Computational & Structural Biology, Houston, TX.. (October 13, 2006) With Tworowska, I.


    "title." 10th Structural Biology Symposium, UTMB. (Galveston, Texas) With May 20-21, 2005


    "title." Nucleic Acids Gordon Conference, Newport, Rhode Island. (June 5-10, 2005)


    "--." RNA '04, 9th Annual Meeting of the RNA Society, Madison, Wisconsin. (June 2-6, 2004)


    "--." 15th Triennial Conference for the International Symposium on Magnetic Resonance, Ponte Vedra, Florida. (October 25-29, 2004)


    "--." 2nd Annual Meeting of Region VII RCE, Dallas, Texas. (December 15-16, 2004)


    Presenter.  "Interaction of DMAPP:tRNA Prenyltransferase with Escherichia coli tRNAPhe." 13th Conversation on Nucleic Acids, Albany, NY. (6/18/03-6/21/03) With Tworowska, I. and Cabello, J.


    P.I..  "NMR Structure Determination of the Anticodon Stem-loop of Escherichia coli tRNAPhe." 13th Conversation on Nucleic Acids, Albany, NY. (6/18/03-6/21/03) With Tworoska, I.


    P.I..  "NMR Structure and Dynamics of the ACSL of tRNAPhe." Nucleic Acids Gordon Conference, Newport, RI. (6/1/03-6/6/03) With Tworowska, I.


    Presenter.  "STRUCTURAL EFFECTS OF SEQUENTIAL BASE MODIFICATIONS IN E. COLI ACSLPHE." 20th International tRNA Conference, Banz, Germany. (10/2/03-10/7/03) With Tworowska, I. and Cabello, J.


    P.I..  "The Structure and Dynamics of Modified Anticodon Stem-Loop of Escherichia coli tRNAPhe." 39th IUPAC Conference, Ottowa, Canada. (8/10/03-8/15/03) With Tworowska, I.


    Presenter.  "Anticodon Stem-loop of E. coli tRNAPhe: N6-Dimethylallyl & Cobalt-hexamine Dependent Conformational Changes." Nucleic Acids Gordon Research Conference, Bristol, R.I.. (June 1-7, 2002) With Javier Cabello, Izabella Tworowska


    Doctoral advisor of O'Neil.  "Structural Investigations of Helix 35 pseudouridine 746 of the 23S rRNA of Escherichia coli Using NMR Spectroscopy." XXth ICMRBS, Toronto, Canada. (8/16-22/2002) With Erin O'Neil (Presenter), Jerome Boisbouvier, Ad Bax

     Seminar Speaker

     “Structural and Mechanistic Studies of Bacterial Regulatory RNAs and Ligands”. Iowa State University, Ames, IA, November 17, 2016.


    "Structural and Mechanistic Studies of Bacterial Regulatory RNAs and Ligands." Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX. (November 20, 2014)

    Supervised Theses & Dissertations
     Jie Xiao, Ph.D. Structural Characterization and Kinetic Evaluation of RecA-Mediated Strand Exchange. (2002) (Thesis Committee Member)

     Michael Berger, Ph.D. The Molecular Bases of Tryptophan Replacement Effects in RecA: A Biochemical and Biophysical Characterization of Single- and Null-Tryptophan Mutant Escherichia coli RecA Proteins. (2002) (Thesis Committee Member)

     Lucian Smith, Ph.D. The Effects of Amino Acid Substitution on Apomyoglobin Stability, Folding Intermediates, and Holoprotein Expression. (2002) (Thesis Committee Member)

     Wei Zhang, Ph.D. X-ray Structural Determination and Biophysical Characterization of HemAT, a Chemotaxis Receptor from B. subtilis. (2003) (Thesis Committee Member)

     Erin O'Neil-Cabello, Ph.D. Methodological Developments for Measuring Residual Dipolar Couplings and 31P Chemical Shift Anisotropy Including Structural Applications, Using Ribosomal Helix-35psi746 as a Model Molecule. (2004) (Thesis Director)

     Beth E. Jackson, Ph.D. Yeast as a Host for Sesquiterpene Production. (2004) (Thesis Committee Member)

     Michelle K. Calabretta, Ph.D. Biophysical Characterization of Gold Nanocrystal Protein Conjugates: Formation, Stoichiometry and Function. (2005) (Thesis Committee Member)

     Samuel Campos, Ph.D. Metabolic Biotinylation of the Adenoviral Capsid: Avidin-Based Applications and Studies of Ligand-Targeted Gene Delivery. (2005) (Thesis Committee Member)

     Rafael Counago, Ph.D. Single Gene Evolution: A Punctuated History of Chance. (2005) (Thesis Committee Member)

     Jinhua Pan, Ph.D. Structural and Functional Studies on Birnavirus RNA Polymerases - Insights into the Protein-priming Mechanism and Evolution of RNA Viruses. (2007) (Thesis Committee Member)

     George Blouin, Ph.D. Alkyl Isocyanides as Transition State Analogs for Ligand Entry and Exit in Globins. (2007) (Thesis Committee Member)

     Hong Zhou, Ph.D. Effect of Nonsteroidal Anti-inflammatory Drugs on the Mechanical and Electrical Stability of Phospholipid Membranes. (2007) (Thesis Committee Member)

     Endah Sulistijo, Ph.D. Specificity of Membrane Helix-Helix Interactions by Mutagenesis and Structural Analysis. (2007) (Thesis Committee Member)

     Megan Guelker, Ph.D. Overcoming the Challenges of Twinning and Pseudo Symmetry in Solving the Structure of Flavodoxin from Desulfovibrio desulfuricans 29577 by X-ray Crystallography. (2008) (Thesis Committee Member)

     Gorge Blouin, Ph.D. Alkyl Isocyanides as Transition State Analogs for Ligand Entry and Exit in Globins. (2008) (Thesis Committee Member)

     Todd Jaszewski, Ph.D. Specificity of Transmembrane Domain Self-association by Mutagenesis and Protein Design. (2008) (Thesis Committee Member)

     Ian Dews, Ph.D. The Four Syndecans: A Fugue in GxxxG Minor. (2008) (Thesis Committee Member)

     Andria Denmon, Ph.D. The Role of Base Modification on Tyrosyl-tRNA Thermodynamics, Structure, and Function in Bacillus subtilis and Bacillus anthracis. (2013) (Thesis Director)

     Andrew Chang, PhD The T Box Mechanism and Anticodon Stem-Loops: Molecular and Structural Studies of Glycyl-tRNA Anticodon Stem-Loops and Their Binding to the T Box Specifier Domain. (2014) (Thesis Director)

     Jonathan Dornell, PhD Interkingdom Interactions between CandidaCandida albicans and Oral Anaerobes in Mixed-Species Biofilms. (2016) (Thesis Committee Member)

     Jerry Wang, PhD Developing an Enzyme Toolbox for Anti-Tumor Natural Product Biosynthesis. (2016) (Thesis Committee Member)

     Fenbeng Wang, PhD Structural characterization of enzymes involved in the biosynthesis of anti-tumor natural products. (Thesis Committee Member)

     Lu Han, PhD Method development for natural products structure determination. (Thesis Committee Member)

    Awards, Prizes, & Fellowships
     Member, American Chemical Society,

     Member, American Association for the Advancement of Science,

     Member, American Association for the Advancement of Science

     Attendee, Robert A. Welch Foundation Meeting, Houston, Texas (October 23-24, 2000)

     Member, American Chemical Society

    Positions Held
     Member, National Science Foundation Study Section, CLP. (2015 - 2015)

     Member, American Chemical Society. (1996 - 2015)