Structure Function Group
3-Dimensional Structural Characterization
- Lars C. Pedersen, Ph.D.
Director, X-ray Crystallography Core Laboratory
- Tel 984-287-3538
- P.O. Box 12233Mail Drop F3-09Durham, N.C. 27709
The main objective of the Structure Function Research Group in the Genomic Integrity and Structural Biology Laboratory (GISBL) is to provide a resource to the NIEHS community that allows for 3-dimensional structural characterization of macromolecules using molecular biology, biochemistry and X-ray crystallographic techniques.
Over the last few years, our main areas of research have focused on heparan sulfate/heparin biosynthesis, DNA repair, bacterial nucleases as virulence factors, and comparative studies of allergens. However, our focus continuously evolves to meet the needs of NIEHS investigators.
Recent areas of research:
- Heparan Sulfate/heparin biosynthesis:
Sulfation at specific hydroxyls and amines along the polysaccharide chain confers specificity for heparan sulfate binding in various processes such as organogenesis, blood coagulation, growth factor/cytokine action, lipid metabolism, and viral infection. The sulfation along the heparan sulfate chain is carried out by individual sulfotransferases that recognize specific saccharide sequence and conformational targets. We are interested in understanding the substrate recognition mechanisms of these enzymes for use in drug synthesis using a chemoenzymatic process.
- DNA repair:
In support of research conducted in the Genomic Integrity and Structural Biology Laboratory, we have been studying the X-family polymerases µ and λ to understand their roles in DNA repair processes such as base excision repair and non-homologous end joining
- Bacterial Nucleases:
Nucleases such as NucA from S. agalactiae, EndA from S. Pneumoniae, and NucA from Anabaena sp. are bacterial extracellular nucleases that are required for full virulence during infection. These DXGH motif enzymes are capable of degrading neutrophil extracellular traps (NETS), a component of the host’s innate immune response, aiding in the bacterial invasion process. As virulence factors, these enzymes could represent targets for the development of novel antibacterial therapeutics.
- Allergen Studies:
In support of research conducted in the London lab, we have been studying crystal structures of allergens from dust mites and cockroaches as well as the major peanut allergen Ara h 2 to better understand how they elicit an immune response.
Lars C. Pedersen, Ph.D., heads the Structure & Function Research Group within the Genomic Integrity and Structural Biology Laboratory. Pedersen is also an Adjunct Associate Professor at the University of North Carolina in Chapel Hill in the School of Pharmacy. He received his Ph.D. in biochemistry from the University of Washington in Seattle in 1994. He joined the NIEHS in 1996 as a postdoctoral fellow in the laboratory of Masahiko Negishi, Ph.D., in the Laboratory of Reproductive and Developmental Toxicology and started the Structure & Function Research Group in the Laboratory of Structural Biology in 2002.