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Full-Text Articles in Physical Sciences and Mathematics

Iapp Aggregation And Cellular Toxicity Are Inhibited By 1,2,3,4,6-Penta-O-Galloyl-Β-D-Glucose, Edward Bruno, Catalina Pereira, Karla P. Roman, Marisa Takiguchi, Pei-Yu Kao, Luiza A. Nogaj, David A. Moffet Mar 2013

Iapp Aggregation And Cellular Toxicity Are Inhibited By 1,2,3,4,6-Penta-O-Galloyl-Β-D-Glucose, Edward Bruno, Catalina Pereira, Karla P. Roman, Marisa Takiguchi, Pei-Yu Kao, Luiza A. Nogaj, David A. Moffet

Chemistry and Biochemistry Faculty Works

The polyphenol, 1,2,3,4,6-penta-O-galloyl-β-D-glucose (PGG) has been found to exhibit a host of positive pharmacologic activities, including anti-cancer and anti-diabetic. Little is known about the mode of action of PGG in yielding these positive activities. We show here that PGG is a potent inhibitor of IAPP (islet amyloid polypeptide, amylin) aggregation. Preventing the initial aggregation event of IAPP is one strategy for slowing, and possibly preventing, the toxic effects of IAPP oligomeric intermediates. Equal molar ratios of PGG to IAPP substantially reduced the ability of IAPP to bind thioflavin T. Atomic force microscopy revealed that PGG prevented amyloid-based fiber formation under …


Yeast Eif4b Binds To The Head Of The 40s Ribosomal Subunit And Promotes Mrna Recruitment Through Its N-Terminal And Internal Repeat Domains, Sarah F. Mitchell Jan 2013

Yeast Eif4b Binds To The Head Of The 40s Ribosomal Subunit And Promotes Mrna Recruitment Through Its N-Terminal And Internal Repeat Domains, Sarah F. Mitchell

Chemistry and Biochemistry Faculty Works

Eukaryotic translation initiation factor (eIF)4B stimulates recruitment of mRNA to the 43S ribosomal pre-initiation complex (PIC). Yeast eIF4B (yeIF4B), shown previously to bind single-stranded (ss) RNA, consists of an N-terminal domain (NTD), predicted to be unstructured in solution; an RNA-recognition motif (RRM); an unusual domain comprised of seven imperfect repeats of 26 amino acids; and a C-terminal domain. Although the mechanism of yeIF4B action has remained obscure, most models have suggested central roles for its RRM and ssRNA-binding activity. We have dissected the functions of yeIF4B's domains and show that the RRM and its ssRNA-binding activity are dispensable in vitro …


Hiv-1 Frameshift Efficiency Is Primarily Determined By The Stability Of Base Pairs Positioned At The Mrna Entrance Channel Of The Ribosome, Kathryn Mouzakis Jan 2013

Hiv-1 Frameshift Efficiency Is Primarily Determined By The Stability Of Base Pairs Positioned At The Mrna Entrance Channel Of The Ribosome, Kathryn Mouzakis

Chemistry and Biochemistry Faculty Works

The human immunodeficiency virus (HIV) requires a programmed -1 ribosomal frameshift for Pol gene expression. The HIV frameshift site consists of a heptanucleotide slippery sequence (UUUUUUA) followed by a spacer region and a downstream RNA stem-loop structure. Here we investigate the role of the RNA structure in promoting the -1 frameshift. The stem-loop was systematically altered to decouple the contributions of local and overall thermodynamic stability towards frameshift efficiency. No correlation between overall stability and frameshift efficiency is observed. In contrast, there is a strong correlation between frameshift efficiency and the local thermodynamic stability of the first 3-4 bp in …