1z7j

From Proteopedia

Human transthyretin (also called prealbumin) complex with 3, 3',5,5'-tetraiodothyroacetic acid (t4ac)

Overview

The crystal structure of the complex of human transthyretin (hTTR) with, 3,3',5,5'-tetraiodothyroacetic acid (T4Ac) has been determined to 2.2, Angstrom resolution. The complex crystallizes in the orthorhombic space, group P2(1)2(1)2, with unit-cell parameters a = 43.46, b = 85.85, c =, 65.44 Angstrom. The structure was refined to R = 17.3% and R(free) = 21.9%, for reflections without any sigma-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.

Disease

Known diseases associated with this structure: Amyloid neuropathy, familial, several allelic types OMIM:[176300], Amyloidosis, senile systemic OMIM:[176300], Carpal tunnel syndrome, familial OMIM:[176300], Dystransthyretinemic hyperthyroxinemia OMIM:[176300]

About this Structure

1Z7J is a Single protein structure of sequence from Homo sapiens with T4A as ligand. This structure superseeds the now removed PDB entry 1KED. Full crystallographic information is available from OCA.

Reference

Ligand binding at the transthyretin dimer-dimer interface: structure of the transthyretin-T4Ac complex at 2.2 Angstrom resolution., Neumann P, Cody V, Wojtczak A, Acta Crystallogr D Biol Crystallogr. 2005 Oct;61(Pt 10):1313-9. Epub 2005, Sep 28. PMID:16204882

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