Integrating molecular probes and molecular dynamics to reveal binding modes of GLUT5 activatory and inhibitory ligands
| Autor: | Christo Z. Christov, Marina Tanasova, Shobhit S. Chaturvedi, Jon Ainsley, Tatyana G. Karabencheva-Christova |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
biology Metals and Alloys Substrate (chemistry) Fructose Transporter General Chemistry Catalysis Surfaces Coatings and Films Electronic Optical and Magnetic Materials Cell membrane 03 medical and health sciences chemistry.chemical_compound Microsecond Molecular dynamics 030104 developmental biology medicine.anatomical_structure chemistry Materials Chemistry Ceramics and Composites medicine biology.protein Biophysics Molecular probe GLUT5 |
| Zdroj: | Chemical communications (Cambridge, England). 54(71) |
| ISSN: | 1364-548X |
| Popis: | Fructose transporter GLUT5 is characterized by unusual substrate specificity and is linked to a variety of metabolic disorders. A series of high-affinity GLUT5-specific sugar-based probes – ManCous – have been very recently described and efficiently used as reporters of GLUT5 activity in cells. Here we present several 1 microsecond molecular dynamics (MD) simulations of GLUT5 and its complexes with fructose and two different ManCou probes, in a solvated cell membrane environment. These simulations show key molecular interactions within GLUT5 that promote the passage of the substrate through vs. blockage of the transport mechanism. Identification of these specific interactions and their long-range effects on GLUT5 structure and dynamics provides an essential basis for the future development of GLUT5-specific inhibitors. |
| Databáze: | OpenAIRE |
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