The human T1R2-T1R3 sweet taste receptor (STR) plays an important role in recognizing various low-molecular-weight sweet-tasting sugars and proteins, resulting in the release of intracellular heterotrimeric G protein ...
The human T1R2-T1R3 sweet taste receptor (STR) plays an important role in recognizing various low-molecular-weight sweet-tasting sugars and proteins, resulting in the release of intracellular heterotrimeric G protein that in turn leads to the sweet taste perception. Xylitol and sorbitol, which are naturally occurring sugar alcohols (polyols) found in many fruits and vegetables, exhibit the potential caries-reducing effect and are widely used for diabetic patients as low-calorie sweeteners. In the present study, computational tools were applied to investigate the structural details of binary complexes formed between these two polyols and the T1R2-T1R3 heterodimeric STR. Principal component analysis revealed that the Venus flytrap domain (VFd) of T1R2 monomer was adapted by the induced-fit mechanism to accommodate the focused polyols, in which α-helical residues 233–268 moved significantly closer to stabilize ligands. This finding likely suggested that these structural transformations might be the important mechanisms underlying polyols-STR recognitions. The calculated free energies also supported the VFd of T1R2 monomer as the preferential binding site for such polyols, rather than T1R3 region, in accord with the lower number of accessible water molecules in the T1R2 pocket. The E302 amino acid residue in T1R2 was found to be the important recognition residue for polyols binding through a strongly formed hydrogen bond. Additionally, the binding affinity of xylitol toward the T1R2 monomer was significantly higher than that of sorbitol, making it a sweeter tasting molecule. [ABSTRACT FROM AUTHOR]
Adipocyte fatty acid-binding protein (AFABP: FABP4) is a member of the intracellular lipid-binding protein family that is thought to target long-chain fatty acids to nuclear receptors such as peroxisome proliferator-a...
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Potentially useful in the treatment of neurodegenerative disorders, Kaempferia parviflora and Myristica fragrans have been shown to possess a wide spectrum of neuropharmacological activities and neuroprotective effect...
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We present a parameterized analytical model of alchemical molecular binding. The model describes accurately the free energy profiles of linear single-decoupling alchemical binding free energy calculations. The paramet...
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Stapled peptides have emerged as a new class of therapeutics to effectively target intractable protein–protein interactions. Thus, efficient and versatile methods granting easy access to this class of compounds and e...
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Stapled peptides have emerged as a new class of therapeutics to effectively target intractable protein–protein interactions. Thus, efficient and versatile methods granting easy access to this class of compounds and expanding the scope(s) of the currently available ones are of great interest. Now, a solidphase approach is described for the synthesis of bisthioether stapled peptides with multiple architectures, including single‐turn, double‐turn, anddouble‐stapled macrocycles. This method allows for ligation with all‐hydrocarbon linkers of various lengths, avoiding the use of unnatural amino acids and expensive catalysts, and affords cyclopeptides with remarkable resistance to proteolytic degradation. The potential of this procedure is demonstrated by applying it to generate a stapled peptide that shows potent in vitro inhibition of methyltransferase activity of the polycomb repressive complex 2 (PRC2) of proteins.
In the original publication of this article [1], labelling within Fig. 7a was incorrect. The updated figure is shown below, with 'dMT1' now corrected to read 'dNMT1'.
In the original publication of this article [1], labelling within Fig. 7a was incorrect. The updated figure is shown below, with 'dMT1' now corrected to read 'dNMT1'.
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