BBMB Research Seminars

February 8
Tatyana Igumenova
Department of Biochemistry and Molecular Physics
Columbia University
"Calmodulin and Triosephosphate Isoamerase: Protein Dynamics in Allostery and Catalysis"
1414 Molecular Biology Buidling
4:10 p.m.

BioSketch
Tatyana Igumenova was born and raised in Novosibirsk, Russia.  She completed her undergraduate degree in chemistry at Novosibirsk State University.  In 2003, she received her Ph.D. (with distinction) in chemistry with Ann McDermott from Columbia University for work with Ann McDermott on solid-state NMR of proteins.  From 2003 to 2005, she was an NIH postdoctoral fellow with A. Joshua Wand at the University of Pennsylvania, where she studied the role of fast sidechain dynamics in long-range coupling of allosteric sites in calmodulin.  She is currently an NIH postdoctoral fellow with Arthur G. Palmer, III at Columbia University.

Selected Publications
Igumenova, T. I. & Palmer, A. G. Off-resonance TROSY-selected R1r experiment with improved sensitivity for medium- and high-molecular-weight proteins. Journal of the American Chemical Society 128, 8110-8111 (2006).

Igumenova, T. I., Frederick, K. K. & Wand, A. J. Characterization of the fast dynamics of protein amino acid side chains using NMR relaxation in solution. Chemical Reviews 106, 1672-1699 (2006).

Igumenova, T. I., Lee, A. L. & Wand, A. J. Backbone and side chain dynamics of mutant calmodulin-peptide complexes. Biochemistry 44, 12627-12639 (2005).

Wang, T. Z., Frederick, K. K., Igumenova, T. I., Wand, A. J. & Zuiderweg, E. R. P. Changes in calmodulin main-chain dynamics upon ligand binding revealed by cross-correlated NMR relaxation measurements. Journal of the American Chemical Society 127, 828-829 (2005).

Abstract
The first part of my talk focuses on the investigation of the role of sub-nanosecond dynamics in the long-range coupling of allosteric sites in proteins. The objective was to establish whether the long-range coupling via dynamics is involved in allosteric behavior and whether this coupling is via a specific path or a general effect. The dynamics of backbone amide groups and methyl-bearing sidechains of four diagnostic calmodulin mutants in complex with the 21-residue smMLCKp peptide was investigated using solution NMR 15N and 2H relaxation techniques. It was concluded that both structural and dynamic factors work in concert to produce the observed allosteric response.

The second part of my talk describes the development of a novel NMR pulse sequence called TROSY-selected rotating-frame (TS-R1r) relaxation experiment. This technique relies on destructive relaxation interference between the 15N chemical shielding anisotropy (CSA) and 1H-15N dipole-dipole interactions to quantify conformational exchange processes in high-molecular-weight proteins. TS- R1r experiment was successfully applied to the characterization of the catalytically relevant backbone motions in a 54 kDa enzyme, triosephosphate isomerase, thus exceeding the molecular weight limit of the conventional rotating-frame relaxation experiment by a factor of four.