The overall aim of this project involves the use of nuclear magnetic resonance (NMR) spectroscopy to characterize biological macromolecules and their interaction with compounds of environmental concern. During the past year, we have been involved in collaborative studies with Dr. Linda Luck at Clarkson University, on bacterial periplasmic receptor proteins. These proteins provide a extremely attractive model systems for studying the general problem of receptor-ligand interactions, since they are relatively small and highly soluble. Initial studies on the glucose/galactose receptor (GGR) have involved the structural and dynamic changes which accompany glucose complexation. These investigations have relied to some extent on our recent discovery of dynamic frequency shift perturbations in the multiplets which arise due to scalar coupling with deuterium nuclei. Future work will involve studies with structural analogs, in an effort to determine how broad the receptor sepcificity is, and to determine the molecular basis for the observed specificity. In parallel with these studies, we have continued our theoretical investigations of dynamic frequency shifts, and have extended the treatment to include coupled spin systems involving nuclei of arbitrary spin. The formation of protein adducts by environmental agents involves complex chemical/biochemical/structural interactions which are, at best, incompletely understood. During the past year, we have initiated a program aimed at the characterization of the adducts formed from bromoacetate and other chemicals of environmental interest. The NMR technique is uniquely suited to the characterization of the heterogeneous adducts which can form under typical physiological conditions.
| Wallace, Bret D; Berman, Zachary; Mueller, Geoffrey A et al. (2017) APE2 Zf-GRF facilitates 3'-5' resection of DNA damage following oxidative stress. Proc Natl Acad Sci U S A 114:304-309 |
| Gabel, Scott A; Smith, Cassandra E; Cuneo, Matthew J et al. (2014) Characterization of the redox transition of the XRCC1 N-terminal domain. Structure 22:1754-1763 |
| Gabel, Scott A; DeRose, Eugene F; London, Robert E (2013) XRCC1 interaction with the REV1 C-terminal domain suggests a role in post replication repair. DNA Repair (Amst) 12:1105-13 |
| Loeffler, Paul A; Cuneo, Matthew J; Mueller, Geoffrey A et al. (2011) Structural studies of the PARP-1 BRCT domain. BMC Struct Biol 11:37 |
| Butterfoss, Glenn L; DeRose, Eugene F; Gabel, Scott A et al. (2010) Conformational dependence of 13C shielding and coupling constants for methionine methyl groups. J Biomol NMR 48:31-47 |
| London, Robert E; Wingad, Brett D; Mueller, Geoffrey A (2008) Dependence of amino acid side chain 13C shifts on dihedral angle: application to conformational analysis. J Am Chem Soc 130:11097-105 |
| DeRose, Eugene F; Clarkson, Michael W; Gilmore, Steven A et al. (2007) Solution structure of polymerase mu's BRCT Domain reveals an element essential for its role in nonhomologous end joining. Biochemistry 46:12100-10 |
| DellaVecchia, Matthew J; Merritt, W Keither; Peng, Ye et al. (2007) NMR analysis of [methyl-13C]methionine UvrB from Bacillus caldotenax reveals UvrB-domain 4 heterodimer formation in solution. J Mol Biol 373:282-95 |
| Krahn, Joseph M; Jackson, Michael R; DeRose, Eugene F et al. (2007) Crystal structure of a type II dihydrofolate reductase catalytic ternary complex. Biochemistry 46:14878-88 |
| London, Robert E; Gabel, Scott A (2006) Photoactivated h/d exchange in tyrosine: involvement of a radical anion intermediate. J Am Chem Soc 128:2268-75 |
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