Lab Overview
During the last four years, we have focused our attention on
four major programs (http://kuhn.scripps.edu); detecting cancer
cells in circulation, structural proteomics on cancer drug targets,
structural and functional proteomics of the SARS CoV, and development
of novel approaches in miniaturization, integration and automation
with an aim towards lowering the overall cost of gene to structure
for all researchers. Overall the Kuhn Lab is engaged in developing
novel therapeutics and diagnostics approaches with a focus on
cancer and viral infections.
Highlight
Kumar Saikatendu
The Functional and Structural Proteomics of SARS virus is aimed at determination
of the structure and function of all proteins from the SARS virion and map
the network of interactions with host proteins with the hope of developing
therapeutics. We have so far determined five crystal structures. These are
those of the ADP-ribose-1”-phosphatase (nsp3b), nsp10, a monomeric
form of nsp15, the PLpro, and the N protein (nucleocapsid). Combined with
the three NMR structures solved by our collaborator Prof. Kurt Wüthrich,
this project has yielded critical structural information on the SARS proteome.
These structures have led to important insights on the function of these
proteins, especially the role of the different components of the replicase
complex, a molecule of unparalled complexity. The structure of N protein,
the primary protein component of the viral nucleocapsid in two different
crystal forms has provided clues on the supramolecular organization of the
polymeric nucleoprotein complex.
The global SARS structure effort has resulted in an inordinately large number
of new folds (15 out of 23 domains). It emphasizes the unique nature of coronaviral
proteins at both sequence and tertiary structure levels and hints at the possibility
that these proteins are probably a part of distinct island in fold space.
These studies are beginning to provide important clues on the replicase complex
formation, trans-cription and RNA processing events that are unique to SARS
virion life cycle. Seven other proteins have been successfully expressed in
soluble, folded forms and are in structure determination pipeline. Together,
the results from these studies should enable identification of lead compounds
as effective anti-virals targeted against this disease.
2006 Publications
1. Hsieh HB, et al. High-speed detection of circulating tumor. Biosens Bioelectron
2006;21:1893-9. [PMID: 16464570]
2. Chrencik JE, et al. Structure and thermodynamic…Structure 2006;14:321-30.
[PMID:16472751]
3. Yadav MK, et al. Coiled coils at the edge of configurational…2006;45:4463-73.
[PMID: 16584182]
4. Joseph JS, et al. Crystal structure of nonstructural protein...J Virol 2006;80:7894-901.[PMID
16873246]
5. Chrencik JE, et al. Structural and biophysical characterization…J
Biol Chem 2006;281:28185-92. [PMID: 16867992]
6. Gerdts CJ, et al. Time-controlled microfluidic…Angew Chem Int Ed Engl
2006;45:8156-60. [PMID: 17099920]
7. Neuman BW, et al. Supramolecular architecture…J Virol 2006;80:8918-28.
[PMID: 16873249]
8. Bencharit S, et al. Multisite promiscuity processing…J Mil Biol 2006;363:201-14.
[PMID: 16962139]
9. Marrinucci D, et al. Case study of the morphologic… Human Pathol 2006;38:514-519.
Ephub 2006 Dec 22.
10. Brooun A, et al. Remedial strategies in structural…Protein Expr Purif,
2007;53:51-62. Epub 2006 [PMID: 17275330]
11. Saikatendu KS, et al. Ribonucleocapsid formation …J Virol 2007Jan
17; Epub 2006. [PMID: 17229691]
