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Full-Text Articles in Chemicals and Drugs

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 Jan 2023

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 …


1h And 13c Nmr Assignments For (N-Methyl)-(−)-(Α)-Isosparteinium Iodide And (N-Methyl)-(−)-Sparteinium Iodide, Kavoos Kolahdouzan, O. Maduka Ogba, Daniel J. O'Leary Aug 2018

1h And 13c Nmr Assignments For (N-Methyl)-(−)-(Α)-Isosparteinium Iodide And (N-Methyl)-(−)-Sparteinium Iodide, Kavoos Kolahdouzan, O. Maduka Ogba, Daniel J. O'Leary

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

(‒)-Sparteine (1) and (–)-(α)-isosparteine (2) are members of the lupine alkaloid family.[1-2] Sparteine has found extensive use in asymmetric organic transformations, including lithiations[3] and Pd-catalyzed oxidations.[4-7] (α)-Isosparteine, which can be made from sparteine, has been utilized as a chiral ligand for a limited number of stereoselective reactions.[8-9] The two compounds differ in that 1 displays an exo-endo arrangement of the bridgehead hydrogens at C-11 and C-6, respectively, while 2 retains an exo-exo arrangement of these atoms (Figure 1). This study is focused on assigning 1H chemical shifts and coupling constants and 13C chemical shifts for N-methyl …


Sharp Rna Recognition Motif Optimizations, Extensions, And Mutations For Use In 2d And 3d Nmr Experiments, Shaun M. Christie Jan 2015

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 …


Conformational Selection And Substrate Binding Regulate The Monomer/Dimer Equilibrium Of The C-Terminal Domain Of Escherichia Coli Enzyme I, Vincenzo Venditti, G. Marius Clore Jan 2012

Conformational Selection And Substrate Binding Regulate The Monomer/Dimer Equilibrium Of The C-Terminal Domain Of Escherichia Coli Enzyme I, Vincenzo Venditti, G. Marius Clore

Vincenzo Venditti

The bacterial phosphotransferase system (PTS) is a signal transduction pathway that couples phosphoryl transfer to active sugar transport across the cell membrane. The PTS is initiated by the binding of phosphoenolpyruvate (PEP) to the C-terminal domain (EIC) of enzyme I (EI), a highly conserved protein that is common to all sugar branches of the PTS. EIC exists in a dynamic monomer/dimer equilibrium that is modulated by ligand binding and is thought to regulate the overall PTS. Isolation of EIC has proven challenging, and conformational dynamics within the EIC domain during the catalytic cycle are still largely unknown. Here, we present …


Structure And Thermodynamics Of A Conserved U2 Snrna Domain From Yeast And Human, Dipali G. Sashital, Vincenzo Venditti, Courtney G. Angers, Gabriel Cornilescu, Samuel E. Butcher Jan 2007

Structure And Thermodynamics Of A Conserved U2 Snrna Domain From Yeast And Human, Dipali G. Sashital, Vincenzo Venditti, Courtney G. Angers, Gabriel Cornilescu, Samuel E. Butcher

Vincenzo Venditti

The spliceosome is a dynamic ribonucleoprotein complex responsible for the removal of intron sequences from pre-messenger RNA. The highly conserved 5′ end of the U2 small nuclear RNA (snRNA) makes key base-pairing interactions with the intron branch point sequence and U6 snRNA. U2 stem I, a stem–loop located in the 5′ region of U2, has been implicated in spliceosome assembly and may modulate the folding of the U2 and U6 snRNAs in the spliceosome active site. Here we present the NMR structures of U2 stem I from human and Saccharomyces cerevisiae. These sequences represent the two major classes of U2 …