1LYW

CATHEPSIN D AT PH 7.5

1LYW の概要

• エントリーDOI: 10.2210/pdb1lyw/pdb
• 分子名称: CATHEPSIN D, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, ... (4 entities in total)
• 機能のキーワード: aspartic protease, hydrolase, glycoprotein
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Lysosome: P07339 P07339
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 148789.81

構造登録者

Lee, A.Y.,Gulnik, S.V.,Erickson, J.W. (登録日: 1998-06-30, 公開日: 1999-07-22, 最終更新日: 2024-11-06)

主引用文献

Lee, A.Y.,Gulnik, S.V.,Erickson, J.W.
Conformational switching in an aspartic proteinase.
Nat.Struct.Biol., 5:866-871, 1998

PubMed Abstract: The crystal structure of a catalytically inactive form of cathepsin D (CatDhi) has been obtained at pH 7.5. The N-terminal strand relocates by 30 A from its position in the interdomain beta-sheet and inserts into the active site cleft, effectively blocking substrate access. CatDhi has a five-stranded interdomain beta-sheet and resembles Intermediate 3, a hypothetical structure proposed to be transiently formed during proteolytic activation of the proenzyme precursor. Interconversion between active and inactive forms of CatD is reversible and may be regulated by an ionizable switch involving the carboxylate side chains of Glu 5, Glu 180, and Asp 187. Our findings provide a structural basis for the pH-dependent regulation of aspartic proteinase activity and suggest a novel mechanism for pH-dependent modulation of substrate specificity.

PubMed: 9783744
DOI: 10.1038/2306

実験手法

X-RAY DIFFRACTION (2.5 Å)