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Articles 1 - 6 of 6
Full-Text Articles in Life Sciences
Characterization Of The Catalytic Ck2 Subunits With Substitutions At Residues Involved In Inhibitor Binding, Paul Desormeaux
Characterization Of The Catalytic Ck2 Subunits With Substitutions At Residues Involved In Inhibitor Binding, Paul Desormeaux
Electronic Thesis and Dissertation Repository
CK2 is a constitutively active, ubiquitously expressed and pleiotropic serine/threonine protein kinase that is implicated in many cellular functions including tumorigenesis. CK2 has two catalytic subunits, CK2a and CK2a’, that carry out its function in the cell. Previous studies have indicated that inhibitor-refractory mutants have been effective in recovering residual CK2 activity, in the presence of inhibitors, when compared to wild type CK2. Based on these observations, inhibitor-refractory mutants were created for both CK2a and CK2a’ and tested with various concentrations with two CK2-specific inhibitors, CX-4945 and inhibitor VIII. The CK2a triple mutant (V66A/I174A/H160D) was tested in inducible U2OS Flp-In …
Insights Into Chibby's Structural Elements And Their Interplay In Wnt Signaling Protein-Protein Interactions, Ryan C Killoran
Insights Into Chibby's Structural Elements And Their Interplay In Wnt Signaling Protein-Protein Interactions, Ryan C Killoran
Electronic Thesis and Dissertation Repository
The Wnt/b-catenin signaling pathway is critical to embryonic development and adult tissue homeostasis. Mutations to Wnt signaling components can cause dysregulation of the pathway, leading to various human diseases such as cancer. The partially disordered protein Chibby (Cby) is a conserved nuclear protein that acts as an antagonist in the Wnt/b-catenin signaling pathway. Cby’s antagonism is accomplished via two mechanisms. First, by competing with the Tcf/Lef family of transcription factors, Cby abrogates the b-catenin-mediated transcription of Wnt signaling genes. Moreover, upon phosphorylation on serine 20 by the kinase Akt, Cby forms a complex with the protein 14-3-3 to facilitate the …
The Mitochondrial Calcium Uniporter Is Autoregulated By Cation Binding To The Β-Grasp-Like Matrix Domain, Samuel K. Lee
The Mitochondrial Calcium Uniporter Is Autoregulated By Cation Binding To The Β-Grasp-Like Matrix Domain, Samuel K. Lee
Electronic Thesis and Dissertation Repository
Mitochondrial calcium (Ca2+) uptake plays fundamental roles in various signaling processes. Entry of Ca2+ into the mitochondrial matrix is tightly controlled by the mitochondrial Ca2+ uniporter (MCU) in a higher order complex regulated by inter- and intra-molecular protein-protein interactions. However, the precise mechanisms controlling MCU function and regulation remain largely unknown. I identified a well-folded N-terminal MCU region from residues 72-189, and its crystal structure revealed a β-grasp-like fold with a cluster of acidic residues that facilitates interactions with dibasic cations. Binding of Ca2+ or Mg2+ destabilize this fold and shift the protein towards …
Structure And Function Relationships Between Atpase Family, Aaa Domain Containing Protein 5, Proliferating Cell Nuclear Antigen, And Usp1-Associated Factor 1, Tam T. Bui
Electronic Thesis and Dissertation Repository
The genome is constantly damaged by intracellular and extracellular factors. At sites of DNA damage, replication forks are stalled, leading monoubiquitination of proliferating cell nuclear antigen (PCNA). Monoubiquitination of PCNA promote the switch from regular high-fidelity polymerases to Y-family polymerases for bypassing damaged DNA. Prolonged replication by these polymerases may lead to increased mutagenesis, so tight regulation of this process is required. ATAD5 recruits a deubiquitinase complex consisting of ubiquitin-specific protease 1 (USP1) and USP1-associated factor 1 (UAF1) to control PCNA monoubiquitination. The mechanism by which ATAD5 and PCNA interact has been previously unexplored. We show through biochemical and structural …
Interaction Of Seca With Unfolded Polypeptides, Aliakbar Khalili Yazdi
Interaction Of Seca With Unfolded Polypeptides, Aliakbar Khalili Yazdi
Electronic Thesis and Dissertation Repository
The evolutionarily well-conserved SecA is essential for bacterial post-translational translocation. SecA uses the energy of ATP to drive preproteins through the membrane pore. The functional oligomeric state of SecA and the molecular basis for recognition of unfolded polypeptides by SecA are major unresolved questions that must be addressed to understand preprotein targeting and the molecular mechanics of SecA-mediated translocation. This thesis will address three aspects of these questions. First, the role of unstructured termini in the oligomerization and function of various SecA constructs was elucidated. By re-examining the tetramerization of a truncated SecA construct (SecA-N68), it was shown that the …
Structural And Functional Studies Of The Heptose Modifying Enzymes That Play A Role In Campylobacter Jejuni Virulence., Heba Soliman Barnawi
Structural And Functional Studies Of The Heptose Modifying Enzymes That Play A Role In Campylobacter Jejuni Virulence., Heba Soliman Barnawi
Electronic Thesis and Dissertation Repository
Campylobacter jejuni is a major cause of gastroenteritis in humans. The capsule of some species contains unique modified heptoses. Heptose modification was elucidated for C. jejuni NCTC11168 and 18-176, and novel epimerases and reductases essential for the heptose modification were identified. We hypothesized that heptose modifying enzymes in C. jejuni have specific catalytic residues that allow for substrate and product specificity. Substrate synthesis, structural modeling, point mutations, and enzymatic analysis have been applied to map the active sites. Putative catalytic residues showed substrate and/or product specificity. The epimerases structures were solved by crystallography done by our collaborator. We also hypothesized …