Chemicals and Drugs Commons^™

Enhancing The Conformational Stability Of The Cl-Par-4 Tumor Suppressor Via Site-Directed Mutagenesis, Samjhana Pandey, Krishna K. Raut, Andrea M. Clark, Antoine Baudin, Lamya Djemri, David S. Libich, Komala Ponniah, Steven M. Pascal

Chemistry & Biochemistry Faculty Publications

Intrinsically disordered proteins play important roles in cell signaling, and dysregulation of these proteins is associated with several diseases. Prostate apoptosis response-4 (Par-4), an approximately 40 kilodalton proapoptotic tumor suppressor, is a predominantly intrinsically disordered protein whose downregulation has been observed in various cancers. The caspase-cleaved fragment of Par-4 (cl-Par-4) is active and plays a role in tumor suppression by inhibiting cell survival pathways. Here, we employed site-directed mutagenesis to create a cl-Par-4 point mutant (D313K). The expressed and purified D313K protein was characterized using biophysical techniques, and the results were compared to that of the wild-type (WT). We have …

The Synthesis And Characterization Of Ionic Liquids Using Nitrogen-Based Cations For Transdermal Delivery, Jo Galloway

Honors Theses

The purpose of this research was to explore the synthesis mechanisms of water-soluble ionic liquids with nitrogen-containing cationic bases for future use in transdermal drug delivery and forensic science applications. Ionic liquids are salts with an organic cation and either an organic or inorganic anion. They have asymmetric structures, which means that the molecules don’t pack together as neatly as other salts do, therefore, they don’t crystallize as easily, and their melting points are lower. Ionic liquids have melting points below 100°C, and many are liquid at room temperature. Mechanistic studies reveal that the potency of ILs in enhancing transdermal …

Structural Biology Of The Enterovirus Replication-Linked 5'-Cloverleaf Rna And Associated Virus Proteins, Steven M. Pascal, Ravindranath Garimella, Meghan S. Warden, Komala Ponniah

Chemistry & Biochemistry Faculty Publications

Although enteroviruses are associated with a wide variety of diseases and conditions, their mode of replication is well conserved. Their genome is carried as a single, positive-sense RNA strand. At the 5′ end of the strand is an approximately 90-nucleotide self-complementary region called the 5′ cloverleaf, or the oriL. This noncoding region serves as a platform upon which host and virus proteins, including the 3B, 3C, and 3D virus proteins, assemble in order to initiate replication of a negative-sense RNA strand. The negative strand in turn serves as a template for synthesis of multiple positive-sense RNA strands. Building on structural …

Sharp Rna Recognition Motif Optimizations, Extensions, And Mutations For Use In 2d And 3d Nmr Experiments, Shaun M. Christie

Williams Honors College, Honors Research Projects

SMRT/HDAC Associated Repressor Protein interacts with the long noncoding RNA, produced by SRA, by binding at the RRMs. Three projects were done to prepare the truncated proteins for use in 2D and 3D NMR experiments. The first focuses on RRM 3 and its optimization during the purification process. The second focuses on RRM 2-4, which was found to be missing two alpha helices that may be important for protein stability. These helices can also interact with RRM 3 as well due to the tight association of RRMs 3 and 4. The two step PCR extension of RRM 2-4 was assumed …

Dysfunctional Conformational Dynamics Of Protein Kinase A Induced By A Lethal Mutant Of Phospholamban Hinder Phosphorylation, Jonggul Kim, Larry R. Masterson, Alessandro Cembran, Raffaello Verardi, Lei Shi, Jiali Gao, Susan S. Taylor, Gianluigi Veglia

Larry Masterson