The objective of the overall research in this laboratory is centered on achieving as complete a description as possible for the structures of peptides, proteins, nucleic acids and their complexes in solution, principally by NMR spectroscopy. At present particular emphasis is being placed on developing approaches which allows the investigation of larger and more complex systems, and increases the precision with which these solution structures can be obtained, as well as on studies aimed at correlating structure and function. Structures for several proteins have been determined and analyzed. These include the cytokine interleukin-4, the complex of calmodulin with a target peptide from skeletal muscle myosin light chain kinase, the double zinc finger domain of the human enhancer binding protein MBP-1, and the E3 binding domain of the dihydrolipoamide succinyl transferase core from the 2-oxoglutarate dehydrogenase multienzyme complex of (italic) E. coli. These studies have exploited many novel 3D and 4D heteronuclear NMR experiments to dramatically increase spectral resolution and thereby resolve assignment ambiguities in larger proteins. The location and effect of structural water in the IgG binding domain of Streptococcal protein G has been investigated and has provided the first demonstration of a water induced distortion of a helix in solution. Finally, a detailed analysis of the electrostatic properties of human thioredoxin has been carried out and related to its structure.
NIH ExPorter
NIH ExPorter