4n86 › Citations

Crystal structures of human transthyretin complexed with glabridin.

Yokoyama T, Kosaka Y, Mizuguchi M
J Med Chem 57 1090-6 (2014)
Related entries: 4n85, 4n87

Cited: 14 times
EuropePMC logo PMID: 24422526

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.

Reviews - 4n86 mentioned but not cited (1)

  1. Natural compounds as inhibitors of transthyretin amyloidosis and neuroprotective agents: analysis of structural data for future drug design. Ciccone L, Tonali N, Nencetti S, Orlandini E. J Enzyme Inhib Med Chem 35 1145-1162 (2020)

Articles - 4n86 mentioned but not cited (1)

  1. Exosomal Transport of Hepatocyte-Derived Drug-Modified Proteins to the Immune System. Ogese MO, Jenkins RE, Adair K, Tailor A, Meng X, Faulkner L, Enyindah BO, Schofield A, Diaz-Nieto R, Ressel L, Eagle GL, Kitteringham NR, Goldring CE, Park BK, Naisbitt DJ, Betts C. Hepatology 70 1732-1749 (2019)


Reviews citing this publication (1)

  1. Review on the Diverse Biological Effects of Glabridin. Zhang J, Wu X, Zhong B, Liao Q, Wang X, Xie Y, He X. Drug Des Devel Ther 17 15-37 (2023)

Articles citing this publication (11)

  1. A new crystal form of human transthyretin obtained with a curcumin derived ligand. Polsinelli I, Nencetti S, Shepard W, Ciccone L, Orlandini E, Stura EA. J Struct Biol 194 8-17 (2016)
  2. Glabridin, an isoflavan from licorice root, upregulates paraoxonase 2 expression under hyperglycemia and protects it from oxidation. Yehuda I, Madar Z, Leikin-Frenkel A, Szuchman-Sapir A, Magzal F, Markman G, Tamir S. Mol Nutr Food Res 60 287-299 (2016)
  3. Human TTR conformation altered by rhenium tris-carbonyl derivatives. Ciccone L, Policar C, Stura EA, Shepard W. J Struct Biol 195 353-364 (2016)
  4. The flavonoid luteolin, but not luteolin-7-O-glucoside, prevents a transthyretin mediated toxic response. Iakovleva I, Begum A, Pokrzywa M, Walfridsson M, Sauer-Eriksson AE, Olofsson A. PLoS One 10 e0128222 (2015)
  5. Ion Mobility-Mass Spectrometry Analysis of Cross-Linked Intact Multiprotein Complexes: Enhanced Gas-Phase Stabilities and Altered Dissociation Pathways. Samulak BM, Niu S, Andrews PC, Ruotolo BT. Anal Chem 88 5290-5298 (2016)
  6. Discovery of γ-Mangostin as an Amyloidogenesis Inhibitor. Yokoyama T, Ueda M, Ando Y, Mizuguchi M. Sci Rep 5 13570 (2015)
  7. Neuroserpin and transthyretin are extracellular chaperones that preferentially inhibit amyloid formation. West J, Satapathy S, Whiten DR, Kelly M, Geraghty NJ, Proctor EJ, Sormanni P, Vendruscolo M, Buxbaum JN, Ranson M, Wilson MR. Sci Adv 7 eabf7606 (2021)
  8. Letter Stability and crystal structures of His88 mutant human transthyretins. Yokoyama T, Hanawa Y, Obita T, Mizuguchi M. FEBS Lett 591 1862-1871 (2017)
  9. Molecular dynamics simulation study of AG10 and tafamidis binding to the Val122Ile transthyretin variant. Morris KF, Geoghegan RM, Palmer EE, George M, Fang Y. Biochem Biophys Rep 21 100721 (2020)
  10. Calcium Binds to Transthyretin with Low Affinity. Cantarutti C, Mimmi MC, Verona G, Mandaliti W, Taylor GW, Mangione PP, Giorgetti S, Bellotti V, Corazza A. Biomolecules 12 1066 (2022)
  11. Glavonoid, a possible supplement for prevention of ATTR amyloidosis. Matsushita H, Isoguchi A, Okada M, Masuda T, Misumi Y, Tsutsui C, Yamaguchi N, Ichiki Y, Sawashita J, Ueda M, Mizuguchi M, Ando Y. Heliyon 7 e08101 (2021)


Quick links