PDBsum entry 1e3f

Transport(thyroxine)

PDB id: 1e3f

Contents

Protein chain

116 a.a. *

Waters ×78

* Residue conservation analysis

PDB id:

1e3f

Name:

Transport(thyroxine)

Title:

Structure of human transthyretin complexed with bromophenols: a new mode of binding

Structure:

Transthyretin. Chain: a, b. Synonym: prealbumin

Source:

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

Biol. unit:

Homo-Tetramer (from PDB file)

Resolution:

1.90Å R-factor: 0.193 R-free: 0.252

Authors:

M.Ghosh,I.A.T.M.Meerts,A.Cook,A.Bergman,A.Brouwer,L.N.Johnson

Key ref:

M.Ghosh et al. (2000). Structure of human transthyretin complexed with bromophenols: a new mode of binding. Acta Crystallogr D Biol Crystallogr, 56, 1085-1095. PubMed id: 10957627 DOI: 10.1107/S0907444900008568

Date:

14-Jun-00 Release date: 29-Aug-00

Protein chains

P02766  (TTHY_HUMAN) -  Transthyretin from Homo sapiens

Seq: 147 a.a.

Struc: 116 a.a.

DOI no: 10.1107/S0907444900008568

Acta Crystallogr D Biol Crystallogr 56:1085-1095 (2000)

PubMed id: 10957627

Structure of human transthyretin complexed with bromophenols: a new mode of binding.

M.Ghosh, I.A.Meerts, A.Cook, A.Bergman, A.Brouwer, L.N.Johnson.

ABSTRACT

The binding of two organohalogen substances, pentabromophenol (PBP) and 2,4,6-tribromophenol (TBP), to human transthyretin (TTR), a thyroid hormone transport protein, has been studied by in vitro competitive binding assays and by X-ray crystallography. Both compounds bind to TTR with high affinity, in competition with the natural ligand thyroxine (T(4)). The crystal structures of the TTR-PBP and TTR-TBP complexes show some unusual binding patterns for the ligands. They bind exclusively in the 'reversed' mode, with their hydroxyl group pointing towards the mouth of the binding channel and in planes approximately perpendicular to that adopted by the T(4) phenolic ring in a TTR-T(4) complex, a feature not observed before. The hydroxyl group in the ligands, which was previously thought to be a key ingredient for a strong binding to TTR, does not seem to play an important role in the binding of these compounds to TTR. In the TTR-PBP complex, it is primarily the halogens which interact with the TTR molecule and therefore must account for the strong affinity of binding. The interactions with the halogens are smaller in number in TTR-TBP and there is a decrease in affinity, even though the interaction with the hydroxyl group is stronger than that in the TTR-PBP complex.

Selected figure(s)

Figure 1.
Figure 1 Schematic diagram of pentabromophenol, 2,4,6-tribromophenol and thyroxine.

Figure 6.
Figure 6 Superposed view of thyroxine on the ligand PBP at the TTR-PBP binding site. (a) In its principal binding mode PBP1, the Br atoms Br2 and Br6 occupy the outer pockets of thyroxine while (b) in the secondary binding mode PBP2, Br3 and Br5 are in the inner pockets of the hormone. I atoms are shown in gold and Br atoms are in rust red. The figures were created using the program XOBJECTS (M. E. M. Noble, unpublished program).

The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2000, 56, 1085-1095) copyright 2000.

Figures were selected by an automated process.