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OCA, Korelly Srivongsana, Léa Wick, Camille Deshayes

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 === Structure ===
+<Structure load='1dvq' size='350' frame='true' align='right' caption='3D structure of human transthyretin (TTR)' scene='3D structure of human transthyretin' />
 Human TTR is a 54 kDa homo-tetramer, described as a dimer of dimer, rich in β-sheet. It is composed of 127 amino acids assembled around the central channel of the protein, resulting in a 222 symmetry protein. This tetramer contains a channel divided into two symmetry-related L-T4-binding sites.
-The channel has three sets of small hydrophobic depressions, termed halogen binding pockets (HBPs). But then, when the side chain of the TTR changes of conformation, these pockets can realise more hydrogen bonds with other molecules, they can be donor or acceptor.  Thus, they are involved in the binding of the natural ligand, the thyroxine (T4).
+The channel has three sets of small hydrophobic depressions, termed halogen binding pockets (HBPs). But then, when the side chain of the TTR changes of conformation, these pockets can realise more hydrogen bonds with other molecules, they can be donor or acceptor.  Thus, they had this name due to their ability to bind the iodines of thyroxine (T4) its natural ligand <ref name="Labaudinière">Labaudinière R. Chapter 9 Discovery and Development of Tafamidis for the Treatment of TTR Familial Amyloid Polyneuropathy. Orphan Drugs and Rare Diseases. Aug 2014 202-229. DOI:https://doi.org/10.1039/9781782624202-00202</ref>.
-At the entry of the binding site, the TTR has a hydrophilic tail, into which the four iodine atoms of the ligand are placed. The innermost binding pocket, HBP-3, is located between the side chains of Ser 117, Thr 119, Ala 108 and Leu 110. Its surface is composed of aliphatic methyl and methylene groups, as well as the Ser 117 hydroxyl group, the carbonyl groups of Ser 117, Thr 118 and Ala 108, and the main chain NH groups of Thr 119, Ala 109 and Leu 110. The central HBP-2 is formed by the side chains of Leu 110, Ala 109, Lys 15, and Leu 17, it is primarily hydrophobic with polar or electrostatic contributions from the carbonyl groups of Lys 15, Ala 108 and Ala 109. The outermost pocket HBP-1 is located between the side chains of Ala 108, Thr 106, Met 13 and Lys 15. This pocket is lined with the methyl and methylene groups of Lys 15, Ala 108 and Thr 106 <ref name= "Klabunde">PMID: 10742177</ref>.
+At the entry of the binding site, the TTR has a hydrophilic tail, into which the four iodine atoms of the ligand are placed. The dimer interface of the TTR is divided in two part, the inner and the outer binding cavity. The innermost binding pocket, HBP-3, is located between the side chains of Ser 117, Thr 119, Ala 108 and Leu 110. Its surface is composed of aliphatic methyl and methylene groups, as well as the Ser 117 hydroxyl group, the carbonyl groups of Ser 117, Thr 118 and Ala 108, and the main chain NH groups of Thr 119, Ala 109 and Leu 110. The central HBP-2 is formed by the side chains of Leu 110, Ala 109, Lys 15, and Leu 17, it is primarily hydrophobic with polar or electrostatic contributions from the carbonyl groups of Lys 15, Ala 108 and Ala 109. The outermost pocket HBP-1 is located between the side chains of Ala 108, Thr 106, Met 13 and Lys 15. This pocket is lined with the methyl and methylene groups of Lys 15, Ala 108 and Thr 106 <ref name= "Klabunde">PMID: 10742177</ref>.
-model 3D 1DVU
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-The dimer interface of the TTR is divided in two part, the inner and the outer binding cavity. The channel forming by dimerization has three symmetric binding pockets on each dimer parts. These pockets are called Halogen-binding pocket (HBPs) due to their ability to bind the iodines of thyroxine <ref name="Labaudinière">Labaudinière R. Chapter 9 Discovery and Development of Tafamidis for the Treatment of TTR Familial Amyloid Polyneuropathy. Orphan Drugs and Rare Diseases. Aug 2014 202-229. DOI:https://doi.org/10.1039/9781782624202-00202</ref>. In the outer cavity are positioned the <scene name='82/829358/Hbp1/2'>HBP1</scene> and <scene name='82/829358/Hbp1prim/2'>HBP1'</scene> pockets, in the inner cavity are placed the <scene name='82/829358/Hbp3/2'>HBP3</scene> and <scene name='82/829358/Hbp3prim/1'>HBP3’</scene> pockets, and the <scene name='82/829358/Hbp2/1'>HBP2</scene> and <scene name='82/829358/Hbp2prim/1'>HBP2’</scene> pockets are at the interface between the inner and outer cavity
 DDBF is bounded according two symmetric equivalent modes <ref name="Petrassi">PMID:15869287</ref>. Indeed, DDBF wears a tricyclic ring system, with 2 hydrogen bond donors and 5 hydrogen bond acceptors, allowing to bound the dimer-dimer interface of the TTR cavity <ref name="National Center for Biotechnology Information">[https://pubchem.ncbi.nlm.nih.gov/compound/Dibenzofuran-4_6-dicarboxylic-acid Link text], PubChem Database. CID:3022(accessed on Dec. 26, 2019).</ref><ref name="Klabunde">PMID:10742177</ref>. Thanks to the complementarity of shape and hydrophobicity, DDBF enters nicely the outer portion of HBPs pockets <ref name="Petrassi "/>. Besides, the tricyclic ring system interacts with <scene name='83/832920/Lys15_leu17_and_ala108/1'>Lys15, Leu17 and Ala108</scene> from two adjacent TTR subunits <ref name="Petrassi"/>.  Additionally, carboxylates at the position 4 and 6 of DDBF make electrostatic interactions at the entrance of <scene name='82/829358/Hbp1/2'>HBP1</scene> and <scene name='82/829358/Hbp1prim/2'>HBP1'</scene>  with <scene name='83/832920/Lys15/3'>Lys15</scene> on the ε-NH3+ groups <ref name="Petrassi"/>.