1Z7J

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

Replaces:  1KED

Summary for 1Z7J

• Entry DOI: 10.2210/pdb1z7j/pdb
• Related: 1PAB 2ROX
• Descriptor: Transthyretin, 3,3',5,5'-TETRAIODOTHYROACETIC ACID (3 entities in total)
• Functional Keywords: albumin, transport, retinol-binding, vitamin a, amyloid, thyroid hormone, liver, plasma, cerebrospinal fluid, polyneuropathy, disease mutation, tetraiodothyroacetic acid, t4ac, prealbumin, transport protein
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P02766
• Total number of polymer chains: 2
• Total formula weight: 29050.38

Authors

Neumann, P.,Wojtczak, A.,Cody, V. (deposition date: 2005-03-25, release date: 2005-06-07, Last modification date: 2023-08-23)

Primary citation

Neumann, P.,Cody, V.,Wojtczak, A.
Ligand binding at the transthyretin dimer-dimer interface: structure of the transthyretin-T4Ac complex at 2.2 Angstrom resolution.
Acta Crystallogr.,Sect.D, 61:1313-1319, 2005

PubMed Abstract: 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.

PubMed: 16204882
DOI: 10.1107/S0907444905022523

Experimental method

X-RAY DIFFRACTION (2.2 Å)