1E3F

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

Summary for 1E3F

• Entry DOI: 10.2210/pdb1e3f/pdb
• Related: 1BM7 1BMZ 1BZ8 1BZD 1BZE 1E4H 1E5A 1ETA 1ETB 1QAB 1RLB 1THA 1THC 1TLM 1TSH 1TTA 1TTB 1TTC 1TTR 1TYR 2PAB 2ROX 2ROY
• Descriptor: TRANSTHYRETIN (2 entities in total)
• Functional Keywords: transport(thyroxine), environmental pollutants, bromophenols
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Secreted: P02766
• Total number of polymer chains: 2
• Total formula weight: 27554.72

Authors

Ghosh, M.,Meerts, I.A.T.M.,Cook, A.,Bergman, A.,Brouwer, A.,Johnson, L.N. (deposition date: 2000-06-14, release date: 2000-08-29, Last modification date: 2023-12-13)

Primary citation

Ghosh, M.,Meerts, I.A.T.M.,Cook, A.,Bergman, A.,Brouwer, A.,Johnson, L.N.
Structure of Human Transthyretin Complexed with Bromophenols : A New Mode of Binding
Acta Crystallogr.,Sect.D, 56:1085-, 2000

PubMed 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.

PubMed: 10957627
DOI: 10.1107/S0907444900008568

Experimental method

X-RAY DIFFRACTION (1.9 Å)