1KGJ

Rat transthyretin (also called prealbumin) complex with 3',5'-dibromoflavone (EMD21388)

1KGJ の概要

• エントリーDOI: 10.2210/pdb1kgj/pdb
• 関連するPDBエントリー: 1GKE 1KED 1KGI 2ROX
• 分子名称: TRANSTHYRETIN, 6,4'-DIHYDROXY-3-METHYL-3',5'-DIBROMOFLAVONE (3 entities in total)
• 機能のキーワード: prealbumin, transport, dibromoflavone, aurone, thyroid hormone, transport protein
• 由来する生物種: Rattus norvegicus (Norway rat)
• 細胞内の位置: Secreted: P02767
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 55308.70

構造登録者

Wojtczak, A.,Neumann, P.,Muziol, T.,Cody, V.,Luft, J.R.,Pangborn, W. (登録日: 2001-11-27, 公開日: 2002-11-27, 最終更新日: 2023-08-16)

主引用文献

Muziol, T.,Cody, V.,Wojtczak, A.
Comparison of binding interactions of dibromoflavonoids with transthyretin.
Acta Biochim.Pol., 48:885-892, 2001

PubMed Abstract: The crystal structure of rat transthyretin (rTTR) complex with the dibromoflavone EMD21388 was determined to 2.3 A resolution and refined to R = 0.203 and Rfree = 0.288. Two different orientations of EMD21388, which differ in the channel penetration by 1.6 A, were found in the A/C binding site of rTTR. The single ligand position observed in the BID site is intermediate between the two positions found in the A/C site. The position of the dibromoflavone in the B/D site is similar to that reported for dibromoaurone in human TTR. The bromine atoms of EMD21388 form strong interactions in the P3 and P3' pockets of rTTR. Due to the different molecular architectures of both ligands, dibromoflavone forms only one interaction with Lys-15 near the channel entrance, while direct interactions with the pair of Lys-15 were reported for dibromoaurone. The C3* methyl group of EMD21388 mediates the bridging interactions between two TTR subunits in the P2 pockets. The interactions of the O2* hydroxyl group of dibromoaurone with the Thr-119 side chain in the P3 pockets are not matched by similar interactions in EMD21388. Both these alternative interactions can explain the competitive binding of 3',5'-dibromoflavonoids to transthyretin.

PubMed: 11995999

実験手法

X-RAY DIFFRACTION (2.3 Å)