Global ETD Search

1	A Hierarchical Graph for Nucleotide Binding Domain 2 Kakraba, Samuel 01 May 2015 (has links) One of the most prevalent inherited diseases is cystic fibrosis. This disease is caused by a mutation in a membrane protein, the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR is known to function as a chloride channel that regulates the viscosity of mucus that lines the ducts of a number of organs. Generally, most of the prevalent mutations of CFTR are located in one of two nucleotide binding domains, namely, the nucleotide binding domain 1 (NBD1). However, some mutations in nucleotide binding domain 2 (NBD2) can equally cause cystic fibrosis. In this work, a hierarchical graph is built for NBD2. Using this model for NBD2, we examine the consequence of single point mutations on NBD2. We collate the wildtype structure with eight of the most prevalent mutations and observe how the NBD2 is affected by each of these mutations. Cystic fibrosis Mutation Graph-theoretic Models NBD2 Molecular Descriptors Nested Graph. Bioinformatics Discrete Mathematics and Combinatorics Epidemiology Other Applied Mathematics
2	Biochemical and Biophysical Studies of Human SUR1 NBD1, Rat SUR2A NBD2 and the Role of the C-terminal Extension in Rat SUR2A NBD1 Alvarez, Claudia Paola 18 March 2013 (has links) SUR2A-mediated regulation of KATP channels is affected by residues belonging to the C terminus of the first nucleotide binding domain (NBD1). We studied the C-terminal region of NBD1 by comparing experiments using NBD1 S615-D914 and NBD1 S615-K972 constructs to studies of NBD1 S615-L933 also performed in our laboratory. Our NMR data suggests that the C-terminal region of NBD1 from residues Q915 to L933 is disordered and transiently contacts the NBD1 core, which may affect NBD1 phosphorylation. Tryptophan quenching fluorescence experiments corroborate that the Q915-L933 C-terminal tail contacts the NBD1 core. Fluorescence thermal denaturation experiments suggest that NBD1 S615-D914 has a higher affinity for MgATP compared with NBD1 S615-L933, implying that the C-terminal tail varies MgATP binding. Additional experiments were performed to identify soluble constructs of hSUR1 NBD1 and rSUR2A NBD2 that would allow detailed biophysical studies of these domains. Some of the constructs studied showed improved solubility and stability. rSUR2A NBD1 hSUR1 NBD1 rSUR2A NBD2 NBDs potassium channel KATP channel NBD1 phosphorylation C-terminal extension Tryptophan quenching Thermal denaturation NMR Regulation of NBD1 Acrylamide quenching Iodide quenching Fluorescence Circular dichroism NBD1 C-terminal tail MgATP binding 0487
3	Biochemical and Biophysical Studies of Human SUR1 NBD1, Rat SUR2A NBD2 and the Role of the C-terminal Extension in Rat SUR2A NBD1 Alvarez, Claudia Paola 18 March 2013 (has links) SUR2A-mediated regulation of KATP channels is affected by residues belonging to the C terminus of the first nucleotide binding domain (NBD1). We studied the C-terminal region of NBD1 by comparing experiments using NBD1 S615-D914 and NBD1 S615-K972 constructs to studies of NBD1 S615-L933 also performed in our laboratory. Our NMR data suggests that the C-terminal region of NBD1 from residues Q915 to L933 is disordered and transiently contacts the NBD1 core, which may affect NBD1 phosphorylation. Tryptophan quenching fluorescence experiments corroborate that the Q915-L933 C-terminal tail contacts the NBD1 core. Fluorescence thermal denaturation experiments suggest that NBD1 S615-D914 has a higher affinity for MgATP compared with NBD1 S615-L933, implying that the C-terminal tail varies MgATP binding. Additional experiments were performed to identify soluble constructs of hSUR1 NBD1 and rSUR2A NBD2 that would allow detailed biophysical studies of these domains. Some of the constructs studied showed improved solubility and stability. rSUR2A NBD1 hSUR1 NBD1 rSUR2A NBD2 NBDs potassium channel KATP channel NBD1 phosphorylation C-terminal extension Tryptophan quenching Thermal denaturation NMR Regulation of NBD1 Acrylamide quenching Iodide quenching Fluorescence Circular dichroism NBD1 C-terminal tail MgATP binding 0487

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