4PME

Human transthyretin (TTR) complexed with ferulic acid and curcumin.

Summary for 4PME

• Entry DOI: 10.2210/pdb4pme/pdb
• Related: 4PM1 4PMF
• Descriptor: Transthyretin, (1Z,4Z,6E)-5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,4,6-trien-3-one, SODIUM ION, ... (6 entities in total)
• Functional Keywords: human transthyretin (ttr) complexes, solubilization of hydrophobic ligands, curcumin degradation, thyroid hormone-binding protein
• Biological source: Homo sapiens (Human)
• Cellular location: Secreted: P02766
• Total number of polymer chains: 2
• Total formula weight: 26764.96

Authors

Stura, E.A.,Ciccone, L. (deposition date: 2014-05-21, release date: 2014-10-08, Last modification date: 2023-09-27)

Primary citation

Ciccone, L.,Tepshi, L.,Nencetti, S.,Stura, E.A.
Transthyretin complexes with curcumin and bromo-estradiol: evaluation of solubilizing multicomponent mixtures.
N Biotechnol, 32:54-64, 2014

PubMed Abstract: Crystallographic structure determination of protein-ligand complexes of transthyretin (TTR) has been hindered by the low affinity of many compounds that bind to the central cavity of the tetramer. Because crystallization trials are carried out at protein and ligand concentration that approach the millimolar range, low affinity is less of a problem than the poor solubility of many compounds that have been shown to inhibit amyloid fibril formation. To achieve complete occupancy in co-crystallization experiments, the minimal requirement is one ligand for each of the two sites within the TTR tetramer. Here we present a new strategy for the co-crystallization of TTR using high molecular weight polyethylene glycol instead of high ionic strength precipitants, with ligands solubilized in multicomponent mixtures of compounds. This strategy is applied to the crystallization of TTR complexes with curcumin and 16α-bromo-estradiol. Here we report the crystal structures with these compounds and with the ferulic acid that results from curcumin degradation.

PubMed: 25224922
DOI: 10.1016/j.nbt.2014.09.002

Experimental method

X-RAY DIFFRACTION (1.264 Å)