Download citation
Download citation
link to html
The crystal structure of the complex of human transthyretin (hTTR) with 3,3′,5,5′-tetraiodothyroacetic acid (T4Ac) has been determined to 2.2 Å resolution. The complex crystallizes in the orthorhombic space group P21212, with unit-cell parameters a = 43.46, b = 85.85, c = 65.44 Å. The structure was refined to R = 17.3% and Rfree = 21.9% for reflections without any σ-cutoff. T4Ac is bound in both the forward and the reverse mode in the two binding sites of hTTR. In the forward orientation, T4Ac binds in a position similar to that described for thyroxine (T4) in the orthorhombic hTTR–T4 complex. In this orientation, the iodine substituents of the phenolic ring are bound in the P3′/P2 halogen pockets. In the reverse orientation, which is the major binding mode of T4Ac, the ligand is bound deep in the TTR channel, with the carboxylic group bound in the P3′ pocket and forming simultaneous polar interactions with the residues constituting the two hormone-binding sites. Such interactions of a thyroxine-analogue ligand bound in the reverse mode have never been observed in TTR complexes previously.

Supporting information

PDB reference: transthyretin–T4Ac complex, 1z7j, r1z7jsf


Follow Acta Cryst. D
Sign up for e-alerts
Follow Acta Cryst. on Twitter
Follow us on facebook
Sign up for RSS feeds