Evgenii Kovrigin

Evgenii Kovrigin (Evgueni Kovriguine), Ph.D.
Assistant Professor
phone: 414-288-7859
email: evgueni.kovriguine@marquette.edu

Biography

Dr. Evgenii Kovrigin (Evgueni Kovriguine) obtained his doctoral degree in Chemistry from the Engelhardt Institute of Molecular Biology (Moscow, Russia) in 1999. His doctoral studies of protein thermodynamics in mixed solvents (at the Institute of Protein Research, Pushchino, Russia) brought him "Microcal Young Scientist Award 1999" presented to him at 2nd International Conference on Applications of Biocalorimetry 1999 (Halle/Saale., Germany). Evgenii's post-doctoral work at UT Southwestern, Dallas and Yale University, New Haven was focused on determination of tertiary structure and dynamic behavior of proteins by means of NMR spectroscopy. From 2006 to 2011, Evgenii was on faculty at the Biochemistry Department of the Medical College of Wisconsin where he focused on dynamics and interactions of proteins involved in cancer signaling pathways (Ras superfamily). He joined the Chemistry Department of Marquette University in the fall of 2011.

Research Interests

Nuclear Magnetic Resonance (NMR) spectroscopy is a multi-faceted tool for chemical, biochemical and biophysical studies. This rapidly developing technique allows probing molecular structure, dynamics and interactions with atomic resolution and in the broadest range of time scales. Our laboratory uses NMR spectroscopy to address important problems in contemporary biophysical chemistry. We complement power of NMR experiments with other approaches such as microcalorimetry, X-ray diffraction, fluorescent and CD-spectroscopy as well as computational techniques.

The major project in the lab focuses on Ras GTPase, a small monomeric G protein. Ras GTPase is the "founding" member of Ras superfamily proteins that are responsible for signal transduction and regulation in a cell. In 2008, we discovered global conformational dynamics in Ras structure (O'Connor, 2008), and now work to identify its structural and functional aspects. Recently, Ras was recognized as a high profile cancer drug target (NIH will be investing $10M a year in finding inhibitors against Ras) that underscores the need for deeper basic understanding of structure and dynamics of this important protein and its homologs.

Another direction in the laboratory is studies of kinetics and thermodynamics in proteins via measurement of NMR line shapes. Complex binding processes in biological molecules often reveal themselves in NMR spectra but quantitative analysis of NMR line shape is a tedious and highly complicated procedure. We are developing algorithms and software for semi-automated analysis of line shapes in NMR spectra with the goal to accelerate research in this field. Current versions of the software for NMR line shape simulation, LineShapeKin Simulation, and fitting of experimental NMR data, Integrative Data Analysis Platform (IDAP), are freely available on my website. Software development continues in collaboration with the Department of Mathematics, Statistics and Computer Science.

Selected Publications

William F. Hawse, Soumya De, Alex I. Greenwood, Linda K. Nicholson, Jaroslav Zajicek, Kristina F. Davis, Evgenii L Kovrigin, K. Christopher Garcia, David M. Kranz, and Brian M. Baker, How a T cell receptor scans peptide/MHC, submitted

Whitney DS, Peterson FC, Kovrigin EL, Volkman BF,  (2013) Allosteric activation of the Par-6 PDZ via a partial unfolding transition, Journal of the American Chemical Society, 135, 9377-9383

O’Connor C, Kovrigin EL (2012) Characterization of the second ion-binding site in the G domain of H-Ras,  Biochemistry, 51, 9638-9646

Gagné D, Charest L-A, Kovrigin EL, and Doucet N, Conservation of flexible residue clusters among structural and functional enzyme homologues (2012) Journal of Biological Chemistry, 287, 44289-44300

De S, Greenwood AI, Rogals M, Kovrigin EL, Lu KP, and Nicholson LK, (2012) Complete Thermodynamic and Kinetic Characterization of the Isomer-Specific Interaction between Pin1-WW Domain and the Amyloid Precursor Protein Cytoplasmic Tail Phosphorylated at Thr66, Biochemistry, 51, 8583-8596

Kovrigin EL (2012) NMR line shapes and multi-state binding equilibria, Journal of Biomolecular NMR, 53, 257-270

Buhrman G., O'Connor C, Zerbe B, Kearney BM, Napoleon R, Kovrigina EA, Vajda S, Kozakov D, Kovrigin EL*, Mattos C, (2011) Analysis of binding site hot spots on the surface of Ras GTPase, Journal of Molecular Biology, Journal of Molecular Biology, 413, 773-789
*) - joint corresponding author

O’Connor C, Kovrigin EL (2011)Assignments of Backbone 1H, 13C and 15N Resonances in H-Ras (1-166) Complexed with GppNHp at Physiological pH, Journal of Biomolecular NMR Assignment 6, 91-93

Greenwood AI, Rogals MJ, De S, Kovrigin EL and Nicholson LK (2011) Complete Determination of the Pin1 Catalytic Domain Thermodynamic Cycle by NMR Lineshape Analysis, Journal of Biomolecular NMR, Journal of Biomolecular NMR, 51, 21-34

Doucet N, Khirich G, Kovrigin EL, and Loria JP (2011)The alteration of hydrogen bonding in the vicinity of histidine 48 disrupts millisecond motions in RNase A, Biochemistry, 50, 1723-1730.

O'Connor C, Kovrigin EL (2008)Global conformational dynamics in Ras. Biochemistry, 47 (39), 10244-10246.
This publication was ranked the top "Most-Accessed Rapid Report in Biochemistry in 2008".

Watt, ED, Shimada, H, Kovrigin, EL, and Loria, JP (2007)"The mechanism of rate-limiting motions in enzyme function.", PNAS, 104, 11981-11986 (2007)
This publication was presented in Research Highlights. Nat. Struct. Mol. Biol., 14, 688.

Kovrigin EL and Loria JP (2006)"Characterization of the transition state of functional enzyme dynamics.", J. Am. Chem. Soc., 128:7724-7725

Kovrigin EL, Kempf JG, Grey MJ, Loria JP (2006)"Faithful Estimation of Dynamics Parameters from CPMG Relaxation Dispersion Measurements", J. Mag. Res., 180:93-104

Kovrigin EL, Loria J (2006)"Enzyme dynamics along the reaction coordinate: Critical role of a conserved residue", Biochemistry 45, 2636-2647

Kim Y, Kovrigin EL, Eletr Z (2006)"NMR studies of Escherichia coli acyl carrier protein: Dynamic and structural differences of the apo- and holo-forms", Biochem. Biophys. Res. Commun. 341: 776-783

Kovrigin EL, Cole R, Loria JP (2003)"Temperature dependence of the backbone dynamics of Ribonuclease A in the ground state and bound to the inhibitor, 5'-phosphothymidine (3'-5')-pyrophosphate adenosine 3'-phosphate."Biochemistry 42: 5279-5291

Chen X, Tomchick DR, Kovrigin E, Arac D, Machius M, Sudhof TC, Rizo J (2002)"Three-dimensional structure of the complexin/SNARE complex."Neuron 33: 397-409

 


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