A new crystal form of human transthyretin obtained with a curcumin derived ligand

作者：Polsinelli Ivan; Nencetti Susanna; Shepard William; Ciccone Lidia; Orlandini Elisabetta; Stura Enrico A^*

来源：Journal of Structural Biology, 2016, 194(1): 8-17.

DOI：10.1016/j.jsb.2016.01.007

• Amyloidosis inhibition
• Natural polyphenols
• High pH transthyretin binding
• Crystal polymorphism
• Crystal packing
• Transthyretin asymmetry

Transthyretin (TTR), a 54 kDa homotetrameric protein that transports thyroxine (T4), has been associated with clinical cases of TTR amyloidosis for its tendency to aggregate to form fibrils. Many ligands with a potential to inhibit fibril formation have been studied by X-ray crystallography in complex with TTR. Unfortunately, the ligand is often found in ambiguous electron density that is difficult to interpret. The ligand validation statistics suggest over-interpretation, even for the most active compounds like diflunisal. The primary technical reason is its position on a crystallographic 2-fold axis in the most common crystal form. Further investigations with the use of polyethylene glycol (PEG) to crystallize TTR complexes have resulted in a new trigonal polymorph with two tetramers in the asymmetric unit. The ligand used to obtain this new polymorph, 4-hydroxychalcone, is related to curcumin. Here we evaluate this crystal form to understand the contribution it may bring to the study of TTR ligands complexes, which are often asymmetric.

• 出版日期2016-4
• 单位中国地震局