Nuclear Magnetic Resonance
DNA Repair Complexes
The goal of the research is to better understand the mechanisms that underlie polymerase fidelity and mutagenesis. Most of the enzymes involved in DNA repair do not act independently, but as part of a highly coordinated response that identifies the type of damage, prepares the damaged site for further biochemistry, and finally resynthesizes the correctly base-paired DNA. Consequently, recent efforts have focused on characterization of the DNA repair complexes that represent the important functional repair unit. Data derived from NMR studies has been integrated with data generated using other techniques, particularly X-ray crystallography and small angle X-ray scattering, in order to extend the range of molecular targets accessible to investigation.
HIV Reverse Transcriptase
With support from the AIDS targeted research program, we have investigated the viral reverse transcriptase (RT) enzyme, which represents an important drug target for the treatment of HIV infection. Recent studies have characterized the complex conformational behavior of RT, and the dimerization process which is required to obtain active enzyme. We are also investigating the Ribonuclease H domain of RT, since at present there are no drugs which specifically target the activity of this domain. A very recent extension of this effort involves the structural characterization of an enzyme from Streptococcus pneumoniae.
Structural Characterization of Allergens
These studies represent an important step in understanding the basis for origins of allergenicity, and for the development of hypoallergenic analogs that can be used for desensitization. Recent successes include determination of two dust mite allergens: Der p 5 and Der p 7, and the major peanut allergen Ara h 2.