3F5N

Structure of native human neuroserpin

3F5N の概要

• エントリーDOI: 10.2210/pdb3f5n/pdb
• 関連するPDBエントリー: 3F02
• 分子名称: Neuroserpin (1 entity in total)
• 機能のキーワード: neuroserpin, serpin, cleaved form, fenib, human, tissue plasminogen activator, hydrolase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: Q99574
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 231601.36

構造登録者

Ricagno, S.,Caccia, S.,Sorrentino, G.,Bolognesi, M. (登録日: 2008-11-04, 公開日: 2009-05-26, 最終更新日: 2023-11-01)

主引用文献

Ricagno, S.,Caccia, S.,Sorrentino, G.,Antonini, G.,Bolognesi, M.
Human neuroserpin: structure and time-dependent inhibition
J.Mol.Biol., 388:109-121, 2009

PubMed Abstract: Human neuroserpin (hNS) is a protein serine protease inhibitor expressed mainly in the nervous system, where it plays key roles in neural development and plasticity by primarily targeting tissue plasminogen activator (tPA). Four hNS mutations are associated to a form of autosomal dominant dementia, known as familial encephalopathy with neuroserpin inclusion bodies. The medical interest in and the lack of structural information on hNS prompted us to study the crystal structure of native and cleaved hNS, reported here at 3.15 and 1.85 A resolution, respectively. In the light of the three-dimensional structures, we focus on the hNS reactive centre loop in its intact and cleaved conformations relative to the current serpin polymerization models and discuss the protein sites hosting neurodegenerative mutations. On the basis of homologous serpin structures, we suggest the location of a protein surface site that may stabilize the hNS native (metastable) form. In parallel, we present the results of kinetic studies on hNS inhibition of tPA. Our data analysis stresses the instability of the hNS-tPA complex with a dissociation half-life of minutes compared to a half-life of weeks observed for other serpin-cognate protease complexes.

PubMed: 19265707
DOI: 10.1016/j.jmb.2009.02.056

実験手法

X-RAY DIFFRACTION (3.15 Å)