Binding of a Pyrene-Based Fluorescent Amyloid Ligand to Transthyretin: A Combined Crystallographic and Molecular Dynamics Study.

ABSTRACT: 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 t

SUBMITTER: Thi Minh NN 

PROVIDER: S-EPMC10405211 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature