Core B is a synthesis, analysis and biochemical core that will provide indispensable services for all three projects. The synthetic component of Core B will carry out scaled-up synthesis, purification and analysis of "tool-kit" and other nucleotide analogs for use in Projects 1 and 3. The biochemical component of Core B is designed to carry out protein purifications and to synthesize specialized DNA constructs required for Projects 1 and 3. The analysis component will be responsible for acquiring and performing global analysis on kinetic data, including presteady state stopped-flow fluorescence intensity and rotational anisotropy, rapid quench experiments, as well as basic NMR and EPR-ENDOR analysis, to be used in support of Projects 2 and 3. Core B will also serve as a primary vehicle for training graduate and postdoctoral students in chemical synthesis and protein purification techniques, the principles and practice of enzyme kinetic analysis, and techniques in experimental NMR and EPR spectroscopy.
Core B provides essential chemical probes, biochemical assays and spectroscopic analysis in support of the three component projects of this Program Project. This work will lead to better understanding of the structure, fidelity and catalytic mechanism of DNA polymerases, and also includes synthesis of compounds to develop a new approach to selective inhibition of cancer-related DNA repair by DNA polymerase beta.
|Hwang, Candy S; Xu, Liang; Wang, Wei et al. (2016) Functional interplay between NTP leaving group and base pair recognition during RNA polymerase II nucleotide incorporation revealed by methylene substitution. Nucleic Acids Res 44:3820-8|
|Kim, Taejin; Freudenthal, Bret D; Beard, William A et al. (2016) Insertion of oxidized nucleotide triggers rapid DNA polymerase opening. Nucleic Acids Res 44:4409-24|
|Oertell, Keriann; Harcourt, Emily M; Mohsen, Michael G et al. (2016) Kinetic selection vs. free energy of DNA base pairing in control of polymerase fidelity. Proc Natl Acad Sci U S A 113:E2277-85|
|JeÅ™Ã¡bek, Petr; FloriÃ¡n, Jan; MartÃnek, VÃ¡clav (2016) Lipid molecules can induce an opening of membrane-facing tunnels in cytochrome P450 1A2. Phys Chem Chem Phys 18:30344-30356|
|Hwang, Candy S; Kung, Alvin; Kashemirov, Boris A et al. (2015) 5'-Î²,Î³-CHF-ATP diastereomers: synthesis and fluorine-mediated selective binding by c-Src protein kinase. Org Lett 17:1624-7|
|Kadina, Anastasia P; Kashemirov, Boris A; Oertell, Keriann et al. (2015) Two Scaffolds from Two Flips: (Î±,Î²)/(Î²,Î³) CH2/NH "Met-Im" Analogues of dTTP. Org Lett 17:2586-9|
|Mukherjee, Shayantani; Bora, Ram Prasad; Warshel, Arieh (2015) Torque, chemistry and efficiency in molecular motors: a study of the rotary-chemical coupling in F1-ATPase. Q Rev Biophys 48:395-403|
|Perera, Lalith; Freudenthal, Bret D; Beard, William A et al. (2015) Requirement for transient metal ions revealed through computational analysis for DNA polymerase going in reverse. Proc Natl Acad Sci U S A 112:E5228-36|
|Freudenthal, Bret D; Beard, William A; Perera, Lalith et al. (2015) Uncovering the polymerase-induced cytotoxicity of an oxidized nucleotide. Nature 517:635-9|
|Frushicheva, Maria P; Mills, Matthew J L; Schopf, Patrick et al. (2014) Computer aided enzyme design and catalytic concepts. Curr Opin Chem Biol 21:56-62|
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