Research & Publications
- Protein Structure, Function, and Design: We are interested in the fundamental question: How does a protein's primary sequence specify its three dimensional structure? In addition, we are investigating the mechanisms by which proteins achieve the exquisite specificity and efficiency that are characteristic of protein-ligand interactions and enzymatic catalysis. Our research focuses upon small proteins, particularly four-helix bundle proteins, that are amenable to study by a variety of biophysical, biochemical and molecular biological techniques.
- Designed Metal-Binding Proteins: We have introduced novel metal-binding sites into two proteins: a designed four-helix bundle protein, a4 and the B1 domain of IgG-binding protein G. The metal-site designs are for both structural and catalytic tetrahedral Zn(II) sites. The structural sites enhance the stability of the proteins, whereas the catalytic sites aim to exploit the powerful nucleophilic activity of Zn(II)- bound water and to mimic natural enzymes such as carbonic anhydrase and carboxypeptidase.
- A Model System to Study b-Sheet Formation: The factors that are important for a-helix formation are much better understood than those for b-sheet formation. This is largely because tractable model systems in which to study b-sheet formation have been lacking. We are using the B1 domain of Ig-binding protein G as an ideal model system in which to study b-sheet formation. We have determined both the intrinsic b-sheet forming propensities of the amino acids and the energetics of pair-wise interactions across two strands of a b-sheet. The results of these studies allow us to formulate the first guidelines for rational b-sheet design.
Specialized Terms: Mental retardation; Protein-protein interactions; Fragile X Mental Retardation Protein (FMRP); Protein-based nanomaterials
Extensive Research Description
Biochemistry; Biophysics; Chemistry; Fragile X Syndrome; Molecular Biology; Fragile X Mental Retardation Protein