High resolution crystal structures of piscine transthyretin reveal different binding modes for triiodothyronine and thyroxine.

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Eneqvist T, Lundberg E, Karlsson A, Huang S, Santos CR, Power DM, Sauer-Eriksson AE

High resolution crystal structures of piscine transthyretin reveal different binding modes for triiodothyronine and thyroxine.

J Biol Chem. 2004 Jun 18;279(25):26411-6. Epub 2004 Apr 13.

PubMed ID
15082720 [ View in PubMed
]
Abstract

Transthyretin (TTR) is an extracellular transport protein involved in the distribution of thyroid hormones and vitamin A. So far, TTR has only been found in vertebrates, of which piscine TTR displays the lowest sequence identity with human TTR (47%). Human and piscine TTR bind both thyroid hormones 3,5,3'-triiodo-l-thyronine (T(3)) and 3,5,3',5'-tetraiodo-l-thyronine (thyroxine, T(4)). Human TTR has higher affinity for T(4) than T(3), whereas the reverse holds for piscine TTR. X-ray structures of Sparus aurata (sea bream) TTR have been determined as the apo-protein at 1.75 A resolution and bound to ligands T(3) and T(4), both at 1.9 A resolution. The apo structure is similar to human TTR with structural changes only at beta-strand D. This strand forms an extended loop conformation similar to the one in chicken TTR. The piscine TTR.T(4) complex shows the T(4)-binding site to be similar but not identical to human TTR, whereas the TTR.T(3) complex shows the I3' halogen situated at the site normally occupied by the hydroxyl group of T(4). The significantly wider entrance of the hormone-binding channel in sea bream TTR, in combination with its narrower cavity, provides a structural explanation for the different binding affinities of human and piscine TTR to T(3) and T(4).

DrugBank Data that Cites this Article

Drug Carriers
DrugCarrierKindOrganismPharmacological ActionActions
LevothyroxineTransthyretinProteinHumans
No
Not AvailableDetails
LiothyronineTransthyretinProteinHumans
Unknown
Not AvailableDetails
LiotrixTransthyretinProteinHumans
Unknown
Not AvailableDetails