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.
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|Alnajjar, Khadijeh S; Garcia-Barboza, Beatriz; Negahbani, Amirsoheil et al. (2017) A Change in the Rate-Determining Step of Polymerization by the K289M DNA Polymerase ? Cancer-Associated Variant. Biochemistry 56:2096-2105|
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|Petruska, John; Goodman, Myron F (2017) Relating DNA base-pairing in aqueous media to DNA polymerase fidelity. Nat Rev Chem 1:|
|Yoon, Hanwool; Warshel, Arieh (2017) Simulating the fidelity and the three Mg mechanism of pol ? and clarifying the validity of transition state theory in enzyme catalysis. Proteins 85:1446-1453|
|Maximoff, Sergey N; Kamerlin, Shina Caroline Lynn; Florián, Jan (2017) DNA Polymerase ? Active Site Favors a Mutagenic Mispair between the Enol Form of Deoxyguanosine Triphosphate Substrate and the Keto Form of Thymidine Template: A Free Energy Perturbation Study. J Phys Chem B 121:7813-7822|
|Yoon, Hanwool; Warshel, Arieh (2016) The control of the discrimination between dNTP and rNTP in DNA and RNA polymerase. Proteins 84:1616-1624|
|Vorobyov, Igor; Kim, Ilsoo; Chu, Zhen T et al. (2016) Refining the treatment of membrane proteins by coarse-grained models. Proteins 84:92-117|
|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|
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