ReferenceID 3596
Crystal structures of human transthyretin complexed with glabridin
J Med Chem
Transthyretin (TTR) is a plasma protein implicated in human amyloid diseases. Several small molecules that bind to the thyroxine-binding site of TTR have been shown to stabilize the TTR tetramer and to inhibit amyloid f
Relationship Network
Interactive first-hop connections across herbs, ingredients, formulas, targets, diseases, symptoms, syndromes, evidence, and monographs.
Click a node to open it in a new tab
Ingredient: 1Reference: 1Links: 1
Arranging relationship network...
Record Fields
Scalar fields from the final reference record.
- Reference Id
- 3596
- Evidence Id
- 20186
- Core Evidence Id
- 20186
- Source Reference Id
- 490
- Herb2 Reference Id
- HBREF000833
- Subject Paper Key
- HBIN027849_24422526
- Pubmed Id
- 24422526
- Doi
- 10.1021/jm401832j
- Paper Title
- Crystal structures of human transthyretin complexed with glabridin
- Paper Abstract
- Transthyretin (TTR) is a plasma protein implicated in human amyloid diseases. Several small molecules that bind to the thyroxine-binding site of TTR have been shown to stabilize the TTR tetramer and to inhibit amyloid fibril formation of TTR. Herein, we demonstrated that glabridin (Glab), a prenylated isoflavan isolated from Glycyrrhiza glabra L., inhibited aggregation of TTR in a thioflavin assay. The TTR-Glab complex structure revealed a novel binding mode including a CH-π interaction with A108 and a hydrogen bond with K15. A structural comparison with the wild type-apo structure revealed that the CH-π interaction with A108 was strengthened by the induced-fit conformational change upon Glab binding. Furthermore, the binding of Glab induced a rotation of the T119 side chain, and the inclusion of a water molecule, leading to stabilization of the dimer-dimer interface. These results demonstrate that Glab is a novel inhibitor of TTR fibrillization and suggest the molecular mechanism by which Glab binding stabilizes the tetramer.
- Journal
- J Med Chem
- Publish Year
- 2014
- Experiment Subject
- Experiment Type
- Others
- Phenotype Related
- Human Amyloid Diseases
- Paper Title Cn
- Paper Title En
- Crystal structures of human transthyretin complexed with glabridin
- Bilingual Status
- semi_complete