3TJO

HtrA1 catalytic domain, mutationally inactivated

3TJO の概要

• エントリーDOI: 10.2210/pdb3tjo/pdb
• 関連するPDBエントリー: 3TJN 3TJQ
• 分子名称: Serine protease HTRA1, octyl beta-D-glucopyranoside, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: peptidase, hydrolase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: Q92743
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 76824.55

構造登録者

Eigenbrot, C.,Ultsch, M. (登録日: 2011-08-24, 公開日: 2012-05-16, 最終更新日: 2024-04-03)

主引用文献

Eigenbrot, C.,Ultsch, M.,Lipari, M.T.,Moran, P.,Lin, S.J.,Ganesan, R.,Quan, C.,Tom, J.,Sandoval, W.,van Lookeren Campagne, M.,Kirchhofer, D.
Structural and Functional Analysis of HtrA1 and Its Subdomains.
Structure, 20:1040-1050, 2012

PubMed Abstract: The homotrimeric human serine protease HtrA1 is homologous to bacterial HtrA proteases regarding the trypsin-like catalytic and PDZ domains but differs by the presence of an N-terminal domain with IGFBP and Kazal homology. The crystal structures and SAXS analysis presented herein reveal the rare tandem of IGFBP- and Kazal-like modules, a protease active site that adopts a competent conformation in the absence of substrate or inhibitor and a model for the intact protein in solution. Highly sensitive enzymatic assays and binding studies demonstrate that the N-terminal tandem has no apparent effect on protease activity, and in accordance with the structure-based predictions, neither the IGFBP- nor Kazal-like module retains the function of their prototype proteins. Our structures of the unliganded HtrA1 active site suggest two-state equilibrium and a "conformational selection" model, in which substrate binds to the active conformer.

PubMed: 22578544
DOI: 10.1016/j.str.2012.03.021

実験手法

X-RAY DIFFRACTION (2.301 Å)