Biochemistry (James R. Williamson, Director)
The Biochemistry Core is located at The Scripps Research Institute and is focused on structural and biochemical characterization of RNA-protein and protein-protein complexes. Facilities for NMR spectroscopy are housed in the Scripps Macromolecular NMR Facility in two dedicated NMR buildings on the Scripps campus. There are currently ten NMR spectrometers operating at fields ranging from 500 MHz to 900 MHz with a variety of capabilities. The NMR laboratory operates as a shared facility between the research groups of Professors Peter Wright, Jane Dyson, Kurt Wüthrich, Jefferey Kelly, and James Williamson. Dr. Gerard Kroon serves as the Assistant Manager of the NMR Facility. In addition to NMR structural studies, the Biochemistry Core is involved in design and implementation of fluorescence assays for RNA-protein and protein-protein interactions, and extending these assays into the HTS format for inhibitor screens. One goal will be to submit validated assays to screening programs, primarily the NIH Molecular Libraries and Screening Centers Network (MLSCN) for true high throughput screening. Hits emerging from these screens will be returned to the original Center members for biological testing. | |
| NMR Solution Structures of HIV RNA-ligand Complexes.
A) The HIV-2 TAR-argininamide complex. The UA-U base triple is highlighted in green, the argininamide analog is shown in red, hydrogen bonding to a G-residue in the major groove, while stacking on an A-residue immediately below the bulge (yellow). B) The Rev-RRE complex. The basic region of Rev forms an alpha helix (red). The RRE (blue) consists of two A-form helices interrupted by an internal loop containing G-A and G-G base pairs. Non-Watson Crick pairs open up the normally restricted major groove to admit the bulky, arginine-rich helical basic region of Rev for specific recognition. These structures were determined in the Williamson lab, in collaboration with Alan Frankel and his colleagues. |
