2rox

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spinqualitylabelsall models 2rox, resolution 2.Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

TRANSTHYRETIN (ALSO CALLED PREALBUMIN) COMPLEX WITH THYROXINE (T4)

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

The molecular structures of two human transthyretin (hTTR, prealbumin), complexes, co-crystallized with thyroxine, (3,5,3',5'-tetraiodo-L-thyronine; T(4)), and with, 3',5'-dinitro-N-acetyl-LL-thyronine (DNNAT), were determined by X-ray, diffraction methods. Crystals of both structures are orthorhombic, space, group P2(1)2(1)2, and have two independent monomers in the asymmetric unit, of the crystal lattice. These structures have been refined to 17.0% for, 8-2.0 A resolution data for the T(4) complex (I), and to R = 18.4% for, 8-2.2 A resolution data for the DNNAT structure (II). This report provides, a detailed description of T(4) binding to wild-type hTTR at 2.0 A, resolution, as well as DNNAT. In both structures, the two independent, hormone-binding sites of the TTR tetramer are occupied by ligand. A 50%, statistical disorder model was applied to account for the crystallographic, twofold symmetry along the binding channel and the lack of such symmetry, for the ligands. Results for the co-crystallized T(4) complex show that, T(4) binds deep in the hormone-binding channel and displaces the bound, water previously reported for T(4) soaked into a native transthyretin, crystal [Blake & Oatley (1977). Nature (London), 268, 115-120]. DNNAT also, binds deeper in the channel toward the tetramer center than T(4) with the, nitro groups occupying the symmetrical innermost halogen pockets. The, N-acetyl moiety does not form polar contacts with the protein side chains, as it is oriented toward the center of the channel. The weak binding, affinity of DNNAT results from the loss of hydrophobic interactions with, the halogen binding pockets as observed in T(4) binding. These data, suggest that the halogen-binding sites toward the tetramer center are of, primary importance as they are occupied by analogues with weak affinity to, TTR, and are therefore selected over the other halogen sites which, contribute more strongly to the overall binding affinity.

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

2ROX is a Single protein structure of sequence from Homo sapiens with SO4 and T44 as ligands. This structure superseeds the now removed PDB entry 1ROX. Full crystallographic information is available from OCA.

Reference

Structures of human transthyretin complexed with thyroxine at 2.0 A resolution and 3',5'-dinitro-N-acetyl-L-thyronine at 2.2 A resolution., Wojtczak A, Cody V, Luft JR, Pangborn W, Acta Crystallogr D Biol Crystallogr. 1996 Jul 1;52(Pt 4):758-65. PMID:15299640

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