The initial transcript of the GLS1 gene undergoes alternative splicing to produce two glutaminase variants (KGA and GAC) that contain unique C-terminal sequences. A truncated form of human glutaminase (hGA(124-551)) that lacks either C-terminal sequence was expressed in E.Coli and purified. This construct exhibits a hyperbolic glutamine saturation profile (K(m) of 1.6 mM). BPTES, bis-2[5-phenylacetamido-1,2,4-thiadiazol-2-yl]ethylsulfide, functions as a potent uncompetitive inhibitor of this construct (K(i) of 0.2 µM). The hGA(124-551) is inactive in the absence of phosphate, but exhibits a hyperbolic phosphate-dependent activation profile that is also inhibited by BPTES. Gel filtration studies indicate that hGA(124-551) forms a dimer in the absence or presence of 100 mM phosphate, whereas addition of BPTES causes the formation of an inactive tetramer. The combined data indicate that BPTES inhibits human glutaminase by a novel mechanism and that BPTES is a potential lead compound for development of an effective cancer chemotherapeutic agent.
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http://dx.doi.org/10.3109/14756366.2011.622272 | DOI Listing |
Sensors (Basel)
December 2024
Department of Electrical and Automation, Shanghai Maritime University, Shanghai 201306, China.
Multi-layer conductive structures, especially those with features like bolt holes, are vulnerable to hidden corrosion and cracking, posing a serious threat to equipment integrity. Early defect detection is vital for implementing effective maintenance strategies. However, the subtle signals produced by these defects necessitate highly sensitive non-destructive testing (NDT) techniques.
View Article and Find Full Text PDFEntropy (Basel)
November 2024
Sony Computer Science Laboratories, Tokyo 141-0022, Japan.
The symmetric Kullback-Leibler centroid, also called the Jeffreys centroid, of a set of mutually absolutely continuous probability distributions on a measure space provides a notion of centrality which has proven useful in many tasks, including information retrieval, information fusion, and clustering. However, the Jeffreys centroid is not available in closed form for sets of categorical or multivariate normal distributions, two widely used statistical models, and thus needs to be approximated numerically in practice. In this paper, we first propose the new Jeffreys-Fisher-Rao center defined as the Fisher-Rao midpoint of the sided Kullback-Leibler centroids as a plug-in replacement of the Jeffreys centroid.
View Article and Find Full Text PDFBiology (Basel)
December 2024
Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT 84132, USA.
Connexins are a family of transmembrane proteins that form membrane channels [...
View Article and Find Full Text PDFMammalian red blood cells are generated via a terminal erythroid differentiation pathway culminating in cell polarization and enucleation. Actin filament polymerization is critical for enucleation, but the molecular regulatory mechanisms remain poorly understood. We utilized publicly available RNA-seq and proteomics datasets to mine for actin-binding proteins and actin- nucleation factors differentially expressed during human erythroid differentiation and discovered that a focal adhesion protein-Tensin-1-dramatically increases in expression late in differentiation.
View Article and Find Full Text PDFExtracellular vesicles (EVs) show great potential for therapeutic delivery to human cells, with a focus on modulating immune responses. The most promising targets for inducing humoral and cellular immunity against a specific antigen are macrophages (Mϕs) and dendritic cells (DCs). Targeting mannose receptors (CD206), which are highly expressed on these antigen-presenting cells, to promote the presentation of specific antigens through EV-mediated uptake, is a promising strategy in clinical immunotherapy.
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