1MZD

crystal structure of human pro-granzyme K

1MZD の概要

• エントリーDOI: 10.2210/pdb1mzd/pdb
• 関連するPDBエントリー: 1MZA
• 分子名称: pro-granzyme K (2 entities in total)
• 機能のキーワード: granzyme, apoptosis, serine protease, s1 family, hydrolase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: P49863
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 26134.19

構造登録者

Hink-Schauer, C.,Estebanez-Perpina, E.,Wilharm, E.,Fuentes-Prior, P.,Klinkert, W.,Bode, W.,Jenne, D.E. (登録日: 2002-10-07, 公開日: 2003-01-14, 最終更新日: 2024-11-20)

主引用文献

Hink-Schauer, C.,Estebanez-Perpina, E.,Wilharm, E.,Fuentes-Prior, P.,Klinkert, W.,Bode, W.,Jenne, D.E.
The 2.2-A Crystal Structure of Human Pro-granzyme K Reveals a Rigid Zymogen with Unusual Features
J.BIOL.CHEM., 277:50923-50933, 2002

PubMed Abstract: Granzyme K (GzmK) belongs to a family of trypsin-like serine proteases localized in electron dense cytoplasmic granules of activated natural killer and cytotoxic T-cells. Like the related granzymes A and B, GzmK can trigger DNA fragmentation and is involved in apoptosis. We expressed the Ser(195) --> Ala variant of human pro-GzmK in Escherichia coli, crystallized it, and determined its 2.2-A x-ray crystal structure. Pro-GzmK possesses a surprisingly rigid structure, which is most similar to activated serine proteases, in particular complement factor D, and not their proforms. The N-terminal peptide Met(14)-Ile(17) projects freely into solution and can be readily approached by cathepsin C, the natural convertase of pro-granzymes. The pre-shaped S1 pocket is occupied by the ion paired residues Lys(188B)-Asp(194) and is hence not available for proper substrate binding. The Ser(214)-Cys(220) segment, which normally provides a template for substrate binding, bulges out of the active site and is distorted. With analogy to complement factor D, we suggest that this strand will maintain its non-productive conformation in mature GzmK, mainly due to the unusual residues Gly(215), Glu(219), and Val(94). We hypothesize that GzmK is proteolytically active only toward specific, as yet unidentified substrates, which upon approach transiently induce a functional active-site conformation.

PubMed: 12384499
DOI: 10.1074/jbc.M207962200

実験手法

X-RAY DIFFRACTION (2.9 Å)