2G9K

Human Transthyretin (TTR) Complexed with Hydroxylated polychlorinated Biphenyl-4-hydroxy-2',3,3',4',5-Pentachlorobiphenyl

2G9K の概要

• エントリーDOI: 10.2210/pdb2g9k/pdb
• 分子名称: Transthyretin, 2',3,3',4',5-PENTACHLOROBIPHENYL-4-OL (3 entities in total)
• 機能のキーワード: ttr, amyloid, transthyretin, hormone-growth factor complex, hormone/growth factor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: P02766
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 28239.58

構造登録者

Palaninathan, S.K.,Smith, C.,Safe, S.H.,Kelly, J.W.,Sacchettini, J.C. (登録日: 2006-03-06, 公開日: 2006-03-14, 最終更新日: 2023-08-30)

主引用文献

Purkey, H.E.,Palaninathan, S.K.,Kent, K.C.,Smith, C.,Safe, S.H.,Sacchettini, J.C.,Kelly, J.W.
Hydroxylated polychlorinated biphenyls selectively bind transthyretin in blood and inhibit amyloidogenesis: rationalizing rodent PCB toxicity
Chem.Biol., 11:1719-1728, 2004

PubMed Abstract: Polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (OH-PCBs) are known to bind to transthyretin (TTR) in vitro, possibly explaining their bioaccumulation, rodent toxicity, and presumed human toxicity. Herein, we show that several OH-PCBs bind selectively to TTR in blood plasma; however, only one of the PCBs tested binds TTR in plasma. Some of the OH-PCBs displace thyroid hormone (T4) from TTR, rationalizing the toxicity observed in rodents, where TTR is the major T4 transporter. Thyroid binding globulin and albumin are the major T4 carriers in humans, making it unlikely that enough T4 could be displaced from TTR to be toxic. OH-PCBs are excellent TTR amyloidogenesis inhibitors in vitro because they bind to the TTR tetramer, imparting kinetic stability under amyloidogenic denaturing conditions. Four OH-PCB/TTR cocrystal structures provide further insight into inhibitor binding interactions.

PubMed: 15610856
DOI: 10.1016/j.chembiol.2004.10.009

実験手法

X-RAY DIFFRACTION (1.85 Å)