1BM7

HUMAN TRANSTHYRETIN (PREALBUMIN) COMPLEX WITH FLUFENAMIC ACID (2-[[3-(TRIFLUOROMETHYL)PHENYL]AMINO] BENZOIC ACID)

1BM7 の概要

• エントリーDOI: 10.2210/pdb1bm7/pdb
• 分子名称: PROTEIN (TRANSTHYRETIN), 2-[[3-(TRIFLUOROMETHYL)PHENYL]AMINO] BENZOIC ACID (3 entities in total)
• 機能のキーワード: thyroxine transport, signaling protein
• 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: 28117.18

構造登録者

Klabunde, T.,Kelly, J.W.,Sacchettini, J.C. (登録日: 1998-07-29, 公開日: 1998-08-05, 最終更新日: 2024-02-07)

主引用文献

Peterson, S.A.,Klabunde, T.,Lashuel, H.A.,Purkey, H.,Sacchettini, J.C.,Kelly, J.W.
Inhibiting transthyretin conformational changes that lead to amyloid fibril formation.
Proc.Natl.Acad.Sci.USA, 95:12956-12960, 1998

PubMed Abstract: Insoluble protein fibrils resulting from the self-assembly of a conformational intermediate are implicated as the causative agent in several severe human amyloid diseases, including Alzheimer's disease, familial amyloid polyneuropathy, and senile systemic amyloidosis. The latter two diseases are associated with transthyretin (TTR) amyloid fibrils, which appear to form in the acidic partial denaturing environment of the lysosome. Here we demonstrate that flufenamic acid (Flu) inhibits the conformational changes of TTR associated with amyloid fibril formation. The crystal structure of TTR complexed with Flu demonstrates that Flu mediates intersubunit hydrophobic interactions and intersubunit hydrogen bonds that stabilize the normal tetrameric fold of TTR. A small-molecule inhibitor that stabilizes the normal conformation of a protein is desirable as a possible approach to treat amyloid diseases. Molecules such as Flu also provide the means to rigorously test the amyloid hypothesis, i.e., the apparent causative role of amyloid fibrils in amyloid disease.

PubMed: 9789022
DOI: 10.1073/pnas.95.22.12956

実験手法

X-RAY DIFFRACTION (2 Å)