2ARY

Catalytic domain of Human Calpain-1

2ARY の概要

• エントリーDOI: 10.2210/pdb2ary/pdb
• 分子名称: Calpain-1 catalytic subunit, CALCIUM ION, BETA-MERCAPTOETHANOL, ... (4 entities in total)
• 機能のキーワード: cysteine protease, papain, calcium-dependent, thiol protease, hydrolase, structural genomics consortium, sgc
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm (By similarity): P07384
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 79551.64

構造登録者

Walker, J.R.,Davis, T.,Lunin, V.,Newman, E.M.,Mackenzie, F.,Weigelt, J.,Sundstrom, M.,Arrowsmith, C.,Edwards, A.,Bochkarev, A.,Dhe-Paganon, S.,Structural Genomics Consortium (SGC) (登録日: 2005-08-22, 公開日: 2005-08-30, 最終更新日: 2023-08-23)

主引用文献

Davis, T.L.,Walker, J.R.,Finerty, P.J.,Mackenzie, F.,Newman, E.M.,Dhe-Paganon, S.
The Crystal Structures of Human Calpains 1 and 9 Imply Diverse Mechanisms of Action and Auto-inhibition
J.Mol.Biol., 366:216-229, 2007

PubMed Abstract: Calpains are calcium activated cysteine proteases found throughout the animal, plant, and fungi kingdoms; 14 isoforms have been described in the human genome. Calpains have been implicated in multiple models of human disease; for instance, calpain 1 is activated in the brains of individuals with Alzheimer's disease, and the digestive tract specific calpain 9 is down-regulated in gastric cancer cell lines. We have solved the structures of human calpain 1 and calpain 9 protease cores using crystallographic methods; both structures have clear implications for the function of non-catalytic domains of full-length calpains in the calcium-mediated activation of the enzyme. The structure of minicalpain 1 is similar to previously solved structures of the protease core. Auto-inhibition in this system is most likely through rearrangements of a central helical/loop region near the active site cysteine, which occlude the substrate binding site. However, the structure of minicalpain 9 indicates that auto-inhibition in this enzyme is mediated through large intra-domain movements that misalign the catalytic triad. This disruption is reminiscent of the full-length inactive calpain conformation. The structures of the highly conserved, ubiquitously expressed human calpain 1 and the more tissue specific human calpain 9 indicate that although there are high levels of sequence conservation throughout the calpain family, isolated structures of family members are insufficient to explain the molecular mechanism of activation for this group of proteins.

PubMed: 17157313
DOI: 10.1016/j.jmb.2006.11.037

実験手法

X-RAY DIFFRACTION (2.4 Å)