4FGU

Crystal structure of prolegumain

4FGU の概要

• エントリーDOI: 10.2210/pdb4fgu/pdb
• 関連するPDBエントリー: 4aw9 4awa 4awb
• 分子名称: Legumain, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• 機能のキーワード: cysteine protease, aep, asparaginyl endopeptidase, substrate specificity, mhcii, antigen processing, proenzyme, cancer, lysosomal, hydrolase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 99702.16

構造登録者

Dall, E.,Brandstetter, H. (登録日: 2012-06-05, 公開日: 2013-07-03, 最終更新日: 2024-11-20)

主引用文献

Dall, E.,Brandstetter, H.
Mechanistic and structural studies on legumain explain its zymogenicity, distinct activation pathways, and regulation.
Proc.Natl.Acad.Sci.USA, 110:10940-10945, 2013

PubMed Abstract: The cysteine protease legumain plays important functions in immunity and cancer at different cellular locations, some of which appeared conflicting with its proteolytic activity and stability. Here, we report crystal structures of legumain in the zymogenic and fully activated form in complex with different substrate analogs. We show that the eponymous asparagine-specific endopeptidase activity is electrostatically generated by pH shift. Completely unexpectedly, the structure points toward a hidden carboxypeptidase activity that develops upon proteolytic activation with the release of an activation peptide. These activation routes reconcile the enigmatic pH stability of legumain, e.g., lysosomal, nuclear, and extracellular activities with relevance in immunology and cancer. Substrate access and turnover is controlled by selective protonation of the S1 pocket (KM) and the catalytic nucleophile (kcat), respectively. The multibranched and context-dependent activation process of legumain illustrates how proteases can act not only as signal transducers but as decision makers.

PubMed: 23776206
DOI: 10.1073/pnas.1300686110

実験手法

X-RAY DIFFRACTION (3.9 Å)