Theses and Dissertations from UMD

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New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a give thesis/dissertation in DRUM

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Author: search.filters.author.Cressman, William JohnSubject: search.filters.subject.Biochemistry

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    Probing Allosteric Communication Between Disordered Surfaces in a Protein
    (2015) Cressman, William John; Beckett, Dorothy; Biochemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Molecular mechanisms of protein allostery are not well understood, particularly in those systems that undergo disorder to order transitions upon activation. BirA, an E.coli metabolic enzyme and transcriptional repressor, is a model allosteric protein in which corepressor, bio-5’-AMP, binding enhances dimerization by -4 kcal/mol and is coupled to disordered loop folding on both functional surfaces. In this work, BirA variants with single alanine substitutions in dimerization surface residues are investigated to further characterize communication between the two sites. Isothermal titration calorimetry (ITC) measurements of corepressor binding of these BirA variants indicate only the G142A substitution perturbs the Gibbs free energy of binding. The G142A crystal structure indicates a mechanism of communication from the corepressor binding to the dimerization surface involving α-helical extension of residues 143-146. Measurements of the heat capacity changes associated with corepressor binding to the BirA variants support a model in which the helical extension enhances dimerization by enabling the formation of a network of intramolecular interactions on the dimerization surface.