Structural analysis of ibuprofen binding to human adipocyte fatty-acid binding protein (FABP4)
| Autor: | Javier M. González, S. Z. Fisher |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Gene isoform
Models Molecular Stereochemistry Biophysics Ibuprofen Crystallography X-Ray Fatty Acid-Binding Proteins Ligands Biochemistry Fatty acid-binding protein Research Communications Hydrophobic effect chemistry.chemical_compound Structural Biology Adipocyte Genetics medicine Humans Binding protein organic chemicals Condensed Matter Physics Small molecule chemistry Selectivity Crystallization medicine.drug |
| Zdroj: | Acta crystallographica. Section F, Structural biology communications. 71(Pt 2) |
| ISSN: | 2053-230X |
| Popis: | Inhibition of human adipocyte fatty-acid binding protein (FABP4) has been proposed as a treatment for type 2 diabetes, fatty liver disease and atherosclerosis. However, FABP4 displays a naturally low selectivity towards hydrophobic ligands, leading to the possibility of side effects arising from cross-inhibition of other FABP isoforms. In a search for structural determinants of ligand-binding selectivity, the binding of FABP4 towards a group of small molecules structurally related to the nonsteroidal anti-inflammatory drug ibuprofen was analyzed through X-ray crystallography. Several specific hydrophobic interactions are shown to enhance the binding affinities of these compounds, whereas an aromatic edge-to-face interaction is proposed to determine the conformation of bound ligands, highlighting the importance of aromatic interactions in hydrophobic environments. |
| Databáze: | OpenAIRE |
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