1MDW

Crystal Structure of Calcium-Bound Protease Core of Calpain II Reveals the Basis for Intrinsic Inactivation

1MDW の概要

• エントリーDOI: 10.2210/pdb1mdw/pdb
• 関連するPDBエントリー: 1AJ5 1ALW 1DFO 1KFU 1KFX 1KXR
• 分子名称: Calpain II, catalytic subunit, CALCIUM ION (3 entities in total)
• 機能のキーワード: calpain cysteine protease fold, two cooperative calcium sites, helix instability, tryptophan-based active site blockage, hydrolase
• 由来する生物種: Rattus norvegicus (Norway rat)
• 細胞内の位置: Cytoplasm (By similarity): Q07009
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 73776.27

構造登録者

Moldoveanu, T.,Hosfield, C.M.,Lim, D.,Jia, Z.,Davies, P.L. (登録日: 2002-08-07, 公開日: 2003-04-29, 最終更新日: 2024-02-14)

主引用文献

Moldoveanu, T.,Hosfield, C.M.,Lim, D.,Jia, Z.,Davies, P.L.
Calpain silencing by a reversible intrinsic mechanism.
Nat.Struct.Biol., 10:371-378, 2003

PubMed Abstract: Uncontrolled activation of calpain can lead to necrotic cell death and irreversible tissue damage. We have discovered an intrinsic mechanism whereby the autolysis-generated protease core fragment of calpain is inactivated through the inherent instability of a key alpha-helix. This auto-inactivation state was captured by the 1.9 A Ca(2+)-bound structure of the protease core from m-calpain, and sequence alignments suggest that it applies to about half of the calpain isoforms. Intact calpain large subunits are also subject to this inhibition, which can be prevented through assembly of the heterodimers. Other isoforms or their released cores are not silenced by this mechanism and might contribute to calpain patho-physiologies.

PubMed: 12665854
DOI: 10.1038/nsb917

実験手法

X-RAY DIFFRACTION (1.95 Å)