Filoviruses, such as Ebola virus require host-cell receptors, endocytosis, proteolytic cleavage, and fusion with the endolysosomal membrane for release of viral material into the cytoplasm. Two-pore channels (TPCs) comprise a subfamily (TPC1-3) of eukaryotic voltage- and ligand-gated cation channels that contain two non-equivalent tandem pore-forming subunits that then dimerize to form quasi-tetramers and orchestrate the trafficking of Filoviruses, including Ebola, in human cells.
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New research reveals the mechanism behind a cancer-relevant inhibition of human sugar transporting protein. The hope is that this will guide future drug design targeting sugar uptake mechanisms. This will ultimately lead to progress in a number of important common conditions, such as diabetes and cancer.
Our group revealed how different inhibitors of the human sugar transporter GLUT1 (figure) bind to a central cavity in the protein to inhibit its function. The results show a surprisingly promiscuous internal binding pocket with submicromolar affinities for chemically distinct substrates. With these results, the hope is that this will guide future drug design targeting sugar uptake mechanisms.
Tumors and cancer cells are highly dependent on sugar uptake to maintain their rapid growth rate. It has been proposed that a regulation or reduction of cellular sugar uptake might have therapeutic benefits. While not being a panacea, a reduction in cancer growth rate could allow other treatments time to reach full effect, and potentially could allow a much improved efficacy of other chemotherapeutics.
Coordinating the impact of structural genomics on the human α-helical transmembrane proteome: This Commentary by 9 membrane centers received 1,327 visits and 2,233 page views since it was published in February 2013. It was ranked #4 in article requests for the month of February.
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