> Detailanzeige

Thi Minh, Nghia Nguyen [VerfasserIn]; Begum, Afshan [VerfasserIn]; Zhang, Jun [VerfasserIn]; Leira, Petter [VerfasserIn]; Todarwal, Yogesh [VerfasserIn]; Linares, Mathieu [VerfasserIn]; Norman, Patrick [VerfasserIn]; Derbyshire, Dean [VerfasserIn]; von Castelmur, Eleonore [VerfasserIn]; Lindgren, Mikael [VerfasserIn]; Hammarström, Per [VerfasserIn]; König, Carolin [VerfasserIn]

Binding of a Pyrene-Based Fluorescent Amyloid Ligand to Transthyretin: A Combined Crystallographic and Molecular Dynamics Study - [published Version]

Literatur-
verwaltung

Zur
Merkliste

Lösche von
Merkliste

Per Whatsapp teilen

Schließen

Merkliste



Sie können Bookmarks mittels Listen verwalten, loggen Sie sich dafür bitte in Ihr SLUB Benutzerkonto ein.
  • Medientyp: Sonstige Veröffentlichung; E-Artikel
  • Titel: Binding of a Pyrene-Based Fluorescent Amyloid Ligand to Transthyretin: A Combined Crystallographic and Molecular Dynamics Study
  • Beteiligte: Thi Minh, Nghia Nguyen [VerfasserIn]; Begum, Afshan [VerfasserIn]; Zhang, Jun [VerfasserIn]; Leira, Petter [VerfasserIn]; Todarwal, Yogesh [VerfasserIn]; Linares, Mathieu [VerfasserIn]; Norman, Patrick [VerfasserIn]; Derbyshire, Dean [VerfasserIn]; von Castelmur, Eleonore [VerfasserIn]; Lindgren, Mikael [VerfasserIn]; Hammarström, Per [VerfasserIn]; König, Carolin [VerfasserIn]
  • Erschienen: Washington, DC : Soc., 2023
  • Erschienen in: Journal of Physical Chemistry B: Biophysics, Biomaterials, Liquids, and Soft Matter 127 (2023), Nr. 30 ; Journal of Physical Chemistry B: Biophysics, Biomaterials, Liquids, and Soft Matter
  • Ausgabe: published Version
  • Sprache: Englisch
  • DOI: https://doi.org/10.15488/15342; https://doi.org/10.1021/acs.jpcb.3c02147
  • ISSN: 1520-6106
  • Schlagwörter: Binding Sites ; Amyloidogenic Proteins ; Amyloidosis ; Humans ; Amyloid
  • Entstehung:
  • Anmerkungen: Diese Datenquelle enthält auch Bestandsnachweise, die nicht zu einem Volltext führen.
  • Beschreibung: Misfolding and aggregation of transthyretin (TTR) cause several amyloid diseases. Besides being an amyloidogenic protein, TTR has an affinity for bicyclic small-molecule ligands in its thyroxine (T4) binding site. One class of TTR ligands are trans-stilbenes. The trans-stilbene scaffold is also widely applied for amyloid fibril-specific ligands used as fluorescence probes and as positron emission tomography tracers for amyloid detection and diagnosis of amyloidosis. We have shown that native tetrameric TTR binds to amyloid ligands based on the trans-stilbene scaffold providing a platform for the determination of high-resolution structures of these important molecules bound to protein. In this study, we provide spectroscopic evidence of binding and X-ray crystallographic structure data on tetrameric TTR complex with the fluorescent salicylic acid-based pyrene amyloid ligand (Py1SA), an analogue of the Congo red analogue X-34. The ambiguous electron density from the X-ray diffraction, however, did not permit Py1SA placement with enough confidence likely due to partial ligand occupancy. Instead, the preferred orientation of the Py1SA ligand in the binding pocket was determined by molecular dynamics and umbrella sampling approaches. We find a distinct preference for the binding modes with the salicylic acid group pointing into the pocket and the pyrene moiety outward to the opening of the T4 binding site. Our work provides insight into TTR binding mode preference for trans-stilbene salicylic acid derivatives as well as a framework for determining structures of TTR-ligand complexes.
  • Zugangsstatus: Freier Zugang