7O50

Crystal structure of human legumain in complex with Gly-Ser-Asn peptide

7O50 の概要

• エントリーDOI: 10.2210/pdb7o50/pdb
• 分子名称: Legumain, GLY-SER-ASN, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: enzyme, cysteine protease, ligase, asparaginyl endopeptidase, substrate, hydrolase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 62209.35

構造登録者

Dall, E.,Brandstetter, H. (登録日: 2021-04-07, 公開日: 2021-09-22, 最終更新日: 2024-10-16)

主引用文献

Dall, E.,Stanojlovic, V.,Demir, F.,Briza, P.,Dahms, S.O.,Huesgen, P.F.,Cabrele, C.,Brandstetter, H.
The Peptide Ligase Activity of Human Legumain Depends on Fold Stabilization and Balanced Substrate Affinities.
Acs Catalysis, 11:11885-11896, 2021

PubMed Abstract: Protein modification by enzymatic breaking and forming of peptide bonds significantly expands the repertoire of genetically encoded protein sequences. The dual protease-ligase legumain exerts the two opposing activities within a single protein scaffold. Primarily localized to the endolysosomal system, legumain represents a key enzyme in the generation of antigenic peptides for subsequent presentation on the MHCII complex. Here we show that human legumain catalyzes the ligation and cyclization of linear peptides at near-neutral pH conditions, where legumain is intrinsically unstable. Conformational stabilization significantly enhanced legumain's ligase activity, which further benefited from engineering the prime substrate recognition sites for improved affinity. Additionally, we provide evidence that specific legumain activation states allow for differential regulation of its activities. Together these results set the basis for engineering legumain proteases and ligases with applications in biotechnology and drug development.

PubMed: 34621593
DOI: 10.1021/acscatal.1c02057

実験手法

X-RAY DIFFRACTION (1.9 Å)