1DVY

CRYSTAL STRUCTURE OF TRANSTHYRETIN IN COMPLEX WITH N-(M-TRIFLUOROMETHYLPHENYL) PHENOXAZINE-4,6-DICARBOXYLIC ACID

1DVY の概要

• エントリーDOI: 10.2210/pdb1dvy/pdb
• 関連するPDBエントリー: 1BMZ 1DVQ 1DVS 1DVT 1DVU 1DVX 1DVZ
• 分子名称: TRANSTHYRETIN, N-(M-TRIFLUOROMETHYLPHENYL) PHENOXAZINE-4,6-DICARBOXYLIC ACID (3 entities in total)
• 機能のキーワード: thyroxine transport, signaling protein, 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: 27257.26

構造登録者

Klabunde, T.,Petrassi, H.M.,Oza, V.B.,Kelly, J.W.,Sacchettini, J.C. (登録日: 2000-01-23, 公開日: 2001-01-23, 最終更新日: 2024-02-07)

主引用文献

Klabunde, T.,Petrassi, H.M.,Oza, V.B.,Raman, P.,Kelly, J.W.,Sacchettini, J.C.
Rational design of potent human transthyretin amyloid disease inhibitors.
Nat.Struct.Biol., 7:312-321, 2000

PubMed Abstract: The human amyloid disorders, familial amyloid polyneuropathy, familial amyloid cardiomyopathy and senile systemic amyloidosis, are caused by insoluble transthyretin (TTR) fibrils, which deposit in the peripheral nerves and heart tissue. Several nonsteroidal anti-inflammatory drugs and structurally similar compounds have been found to strongly inhibit the formation of TTR amyloid fibrils in vitro. These include flufenamic acid, diclofenac, flurbiprofen, and resveratrol. Crystal structures of the protein-drug complexes have been determined to allow detailed analyses of the protein-drug interactions that stabilize the native tetrameric conformation of TTR and inhibit the formation of amyloidogenic TTR. Using a structure-based drug design approach ortho-trifluormethylphenyl anthranilic acid and N-(meta-trifluoromethylphenyl) phenoxazine 4, 6-dicarboxylic acid have been discovered to be very potent and specific TTR fibril formation inhibitors. This research provides a rationale for a chemotherapeutic approach for the treatment of TTR-associated amyloid diseases.

PubMed: 10742177
DOI: 10.1038/74082

実験手法

X-RAY DIFFRACTION (1.9 Å)