Polyproline-II helix in proteins: structure and function.

Isoxazoline containing natural products as anticancer agents: a review.

Fumagillin is the only antibiotic approved for control of nosema disease in honey bees and has been extensively used in United States apiculture for more than 50 years for control of Nosema apis. It is toxic to mammals and must be applied seasonally and with caution to avoid residues in honey. Fumagillin degrades or is diluted in hives over the foraging season, exposing bees and the microsporidia to declining concentrations of the drug. We showed that spore production by Nosema ceranae, an emerging microsporidian pathogen in honey bees, increased in response to declining fumagillin concentrations, up to 100% higher than that of infected bees that have not been exposed to fumagillin. N. apis spore production was also higher, although not significantly so. Fumagillin inhibits the enzyme methionine aminopeptidase2 (MetAP2) in eukaryotic cells and interferes with protein modifications necessary for normal cell function. We sequenced the MetAP2 gene for apid Nosema species and determined that, although susceptibility to fumagillin differs among species, there are no apparent differences in fumagillin binding sites. Protein assays of uninfected bees showed that fumagillin altered structural and metabolic proteins in honey bee midgut tissues at concentrations that do not suppress microsporidia reproduction. The microsporidia, particularly N. ceranae, are apparently released from the suppressive effects of fumagillin at concentrations that continue to impact honey bee physiology. The current application protocol for fumagillin may exacerbate N. ceranae infection rather than suppress it.

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Nosema ceranae Escapes Fumagillin Control in Honey Bees

G-Quadruplexes, noncanonical nucleic acid structures, act as silencers in the promoter regions of human genes; putative G-quadruplex forming sequences are also present in promoters of other mammals, yeasts, and prokaryotes Here we show that also the HIV-1 LTR promoter exploits G-quadruplex-mediated transcriptional regulation with striking similarities to eukaryotic promoters and that treatment with a G-quadruplex ligand inhibits HIV-1 infectivity Computational analysis on 953 HIV-1 strains substantiated a highly conserved G-rich sequence corresponding to Sp1 and NF-κB binding sites Biophysical/biochemical analysis proved that two mutually exclusive parallel-like intramolecular G-quadruplexes, stabilized by small molecule ligands, primarily fold in this region Mutations disrupting G-quadruplex formation enhanced HIV promoter activity in cells, whereas treatment with a G-quadruplex ligand impaired promoter activity and displayed antiviral effects These findings disclose the possibility of inhibiting th

/pdf/a-dynamic-g-quadruplex-region-regulates-the-hiv-1-long-25aw9p171m.pdf

A Dynamic G-Quadruplex Region Regulates the HIV-1 Long Terminal Repeat Promoter

Hydrogen/deuterium exchange (HDX) detected by mass spectrometry (MS) is extraordinarily useful in the study of many aspects of proteins, especially the analysis of protein conformation and dynamics. While once a challenging and therefore sparingly used method, modern HDX MS is more straightforward, rapid, and routine than in the past. As a result, the breadth of applications of the method has expanded. This Review catalogs applications of HDX MS that have appeared in the literature during the 30 months from January 2012 to June 2014. As penetration of the method into nonacademic sectors where confidentiality is necessary is also at an all-time high, many more applications of this method likely exist that have not been reported in the literature.

A synopsis of the recent applications of HDX MS is shown in Figure ​Figure11 where classifications have been made in terms of sector in which the work was performed, geography, and general topic. We elected to categorize the publications in these ways to emphasize that the method is used not only in all sectors but also on nearly every continent. Many different possibilities existed for characterizing the applications by topic, and this was not a perfect task. Some papers belong in multiple topics or could arguably be placed in different categories than we finally decided. An Excel database and an Endnote library of the 234 articles we surveyed, both of which contain the topic groupings, are available from the authors.



Figure 1

Synopsis of the published applications of HDX MS from January 2012 to June 2014. (A) A total of two-hundred thirty-four (234) articles were published and classified according to the scheme shown, based on author affiliations. The number of articles in ...



Academia is the largest sector contributing to published HDX MS applications (Figure ​(Figure1).1). Approximately 25% of the papers surveyed included multiple sectors, which we have classified as mixed. As mentioned above, such categorization is biased against work that has not been published. Industrial research and research from governmental laboratories must/may remain confidential. Therefore, the results in Figure ​Figure1A1A are to be interpreted with this in mind. The United States was the primary source of publications in HDX MS during the January 2012 to June 2014 time period (Figure ​(Figure1B,C),1B,C), although significant and important work originated from 22 other countries (Figure ​(Figure1D).1D). To illustrate the HDX MS applications in much greater detail, we have divided the remainder of the article into six sections that each discuss one of the topical classifications shown in Figure ​Figure11E.

John Jeff Alvarado

Papers

Abstract 2017: Conformation-dependent Inhibition of the AML-associated Src-family kinase Fgr by ATP-site inhibitors