4N6N

Crystal structure of oxidized legumain in complex with cystatin E/M

4N6N の概要

• エントリーDOI: 10.2210/pdb4n6n/pdb
• 関連するPDBエントリー: 4N6L 4N6M 4N6O
• 分子名称: Legumain, Cystatin-M, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• 機能のキーワード: complex, cysteine protease, inhibitor, legumain, asparaginyl endopeptidase, reactive center loop, papain, cathepsin, cancer, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 48260.03

構造登録者

Dall, E.,Brandstetter, H. (登録日: 2013-10-14, 公開日: 2015-02-18, 最終更新日: 2023-11-15)

主引用文献

Dall, E.,Fegg, J.C.,Briza, P.,Brandstetter, H.
Structure and mechanism of an aspartimide-dependent Peptide ligase in human legumain.
Angew.Chem.Int.Ed.Engl., 54:2917-2921, 2015

PubMed Abstract: Peptide ligases expand the repertoire of genetically encoded protein architectures by synthesizing new peptide bonds, energetically driven by ATP or NTPs. Here, we report the discovery of a genuine ligase activity in human legumain (AEP) which has important roles in immunity and tumor progression that were believed to be due to its established cysteine protease activity. Defying dogma, the ligase reaction is independent of the catalytic cysteine but exploits an endogenous energy reservoir that results from the conversion of a conserved aspartate to a metastable aspartimide. Legumain's dual protease-ligase activities are pH- and thus localization controlled, dominating at acidic and neutral pH, respectively. Their relevance includes reversible on-off switching of cystatin inhibitors and enzyme (in)activation, and may affect the generation of three-dimensional MHC epitopes. The aspartate-aspartimide (succinimide) pair represents a new paradigm of coupling endergonic reactions in ATP-scarce environments.

PubMed: 25630877
DOI: 10.1002/anie.201409135

実験手法

X-RAY DIFFRACTION (1.87 Å)