Investigators and Program Directors

Research Interests

Proteins exhibit highly intricate tertiary structures as determined by crystallographic or NMR analysis. Yet these conformations are highly dynamic, and that flexibility is believed to often play a critical role in the biological function. NMR offers an unmatched capability to characterize both the frequency range and amplitude of motion for individual atoms throughout a protein molecule. Our laboratory applies a combination of selective stable isotope enrichment and protein design approaches to enable our NMR experiments to more effectively probe local structural mobility and its propagation through the protein structure.

In recent years there has been substantial success in characterizing the conformational dynamics of the peptide backbone in various proteins by NMR. A comparable level of detail for the sidechain dynamics has been more challenging to obtain. However, the binding of low molecular weight substrates as well as larger macromolecular complexes are primarily mediated through sidechain interactions. Similarly, the specificity of the native tertiary structure results from the differing sequence of sidechains and their mutual interactions. Selective ²H and ¹³C sidechain labeling techniques developed in our lab provide simplification of the nuclear spin interactions so that analogous experiments to those successfully applied to backbone dynamics are amenable to the sidechains as well. We are carrying out NMR measurements on pairs of homologous proteins and on systematically designed hybrids derived from these parental sequences. Such experiments provide insight into how conformational transitions propagate their effects through the protein structure.

Contact Information

Phone: (518) 474-6396
Fax: (518) 473-2900
E-mail: lemaster@wadsworth.org