Evgenii Kovrigin (Evgueni Kovriguine), Ph.D.
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.
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. My 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.
One of the major projects in the lab is focused on small Ras-like GTPases. We aim to identify a functional role for the global conformational dynamics, which we discovered in Ras structure in 2008. There are two major long term goals of this research. First, Ras GTPase is a prototypical example of Ras superfamily proteins responsible for signal transduction and regulation in a cell making it highly important to achieve the best knowledge of Ras possible.The second goal is to understand Ras from chemical and physical viewpoint as a sophisticated molecular machine where motions are ultimately coupled to chemical reactivity and non-covalent interactions with ligands. My belief is that future "nano"-machines will be engineered starting from protein structures to produce versatile, self-assembling and highly tunable molecular devices. Much of fundamental knowledge is still lacking and we are making progress towards both of these goals.
Another direction in the laboratory is the development of computational methods and software for quantitative analysis of experimental data. Often, we study some very complex system and make measurements by different approaches illuminating the system from different "angles". However, integrating these complementary views into a one unified model is not trivial, especially, if NMR line shape and spin relaxation data are involved. In this project we aim to design a user-friendly and portable software platform to enable analysis of variety of measurements such as NMR, calorimetry, enzyme assays, rapid mixing kinetics, etc. in one fitting session. Currently, we have NMR line shape analysis packages developed - available from http://lineshapekin.net/ and http://biophysicslab.net/. Software development continues in collaboration with Department of Mathematics, Statistics and Computer Science.
Buhrman G., O'Connor C, Zerbe B, Kearney BM, Napoleon R, Kovrigina EA, Vajda S, Kozakov D, Kovrigin EL*, Mattos C, Analysis of binding site hot spots on the surface of Ras GTPase, Journal of Molecular Biology, in press
*) - 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, in press
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, in press
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