PDBsum entry 2rox

Transport

PDB id: 2rox

Contents

Protein chain

118 a.a. *

Ligands

SO4

T44 ×2

Waters ×131

* Residue conservation analysis

PDB id:

2rox

Name:

Transport

Title:

Transthyretin (also called prealbumin) complex with thyroxine (t4)

Structure:

Transthyretin. Chain: a, b. Synonym: prealbumin

Source:

Homo sapiens. Human. Organism_taxid: 9606. Organ: plasma. Tissue: plasma

Biol. unit:

Homo-Tetramer (from PDB file)

Resolution:

2.00Å R-factor: 0.170

Authors:

A.Wojtczak,V.Cody,J.R.Luft,W.Pangborn

Key ref:

A.Wojtczak et al. (1996). 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. Acta Crystallogr D Biol Crystallogr, 52, 758-765. PubMed id: 15299640 DOI: 10.1107/S0907444996003046

Date:

23-Oct-96 Release date: 21-Apr-97

Supersedes:

1rox

Protein chains

P02766  (TTHY_HUMAN) -  Transthyretin from Homo sapiens

Seq: 147 a.a.

Struc: 118 a.a.

DOI no: 10.1107/S0907444996003046

Acta Crystallogr D Biol Crystallogr 52:758-765 (1996)

PubMed id: 15299640

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.

A.Wojtczak, V.Cody, J.R.Luft, W.Pangborn.

ABSTRACT

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.

Selected figure(s)

Figure 1.
Fig. 1. The a-carbon representation of the human transthyretin quaternary structure showing the two independent monomeric subunits A and B forming the twofold-related tetramer with monomers labeled A' and B'. The tetramer is projected down the a axis. The van der Waals surface of thyroxine is shown in the TTR-binding sites.

Figure 3.
Fig. 3. Omit (F o -F,) electron-density map, contoured at 5or, for hTTR-T 4 indicating the iodine positions of thyroxine in binding domain A. This model shows that the hormone binds with its phenolic ring near the tetramer center.

The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (1996, 52, 758-765) copyright 1996.

Figures were selected by the author.