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Structural and computational studies of two oligonucleotide modifying enzymes: I-PpoI and T4 polynucleotide kinase
Endonucleases are a large class of enzymes that catalyze the formation of site-specific double strand breaks in DNA. Homing endonucleases are expressed from open reading frames within intervening sequences (introns or inteins) and promote the lateral transfer of their host intron to a cognate intronless allele. A novel mechanism ...
Identifying substrate and E2 interactions of the BRCA1/BARD1 ubiquitin ligase
My thesis project addresses the need to understand the function of the Breast Cancer Susceptibility Protein, BRCA1, during the process of protein ubiquitination. A significant number of known cancer predisposing mutations are found within BRCA1's RING domain which, when associated with BARD1, functions as a ubiquitin ligase. ...
In silico protein evolution by intelligent design: creating new and improved protein structures
Natural proteins perform a startling diversity of biological functions, but comprise a miniscule fraction of the theoretical sequence-structure space that polypeptides might occupy. The goal of protein design is to identify new free-energy minima in this sequence-structure landscape so as to expand the functional repertoire ...
Elimination of zinc from synaptic visicles in the intact mouse brain by targeted disruption of ZnT3
This dissertation demonstrates that zinc is taken up into synaptic vesicles by a mechanism that requires the zinc transporter, ZnT3, at the vesicle membrane and begins to address the physiological importance of synaptic vesicle zinc. In situ hybridization and immunohistochemistry showed that ZnT3 expression is limited to ...
Electrostatic interactions and exciton coupling in photosynthetic light-harvesting complexes and reaction centers
Protein-pigment complexes are integral to many biochemical reactions. The properties of the pigments in these complexes depend in large part on the protein which serves as both scaffold and solvent. The relative positions of the pigments determine the electronic coupling of the system while local protein charges and vibrational ...
Development and validation of statistical potential functions for the prediction of protein/nucleic-acid interactions from structure
This work outlines the development, validation and application of a series of novel statistical (knowledge-based) potential functions to the prediction of protein/nucleic-acid interactions from structure. Three methods are described: a statistical potential for the evaluation of inter-molecular hydrogen bonds at protein/nucleic-acid ...