5L9Z

Crystal structure of human heparanase nucleophile mutant (E343Q), in complex with unreacted glucuronic acid configured aziridine probe JJB355

5L9Z の概要

• エントリーDOI: 10.2210/pdb5l9z/pdb
• 分子名称: Heparanase, 2-acetamido-2-deoxy-beta-D-glucopyranose, 1,2-ETHANEDIOL, ... (7 entities in total)
• 機能のキーワード: heparanase, probe, gh79, hydrolase
• 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: 54043.17

構造登録者

Wu, L.,Jin, Y.,Davies, G.J. (登録日: 2016-06-13, 公開日: 2017-05-31, 最終更新日: 2024-10-23)

主引用文献

Wu, L.,Jiang, J.,Jin, Y.,Kallemeijn, W.W.,Kuo, C.L.,Artola, M.,Dai, W.,van Elk, C.,van Eijk, M.,van der Marel, G.A.,Codee, J.D.C.,Florea, B.I.,Aerts, J.M.F.G.,Overkleeft, H.S.,Davies, G.J.
Activity-based probes for functional interrogation of retaining beta-glucuronidases.
Nat. Chem. Biol., 13:867-873, 2017

PubMed Abstract: Humans express at least two distinct β-glucuronidase enzymes that are involved in disease: exo-acting β-glucuronidase (GUSB), whose deficiency gives rise to mucopolysaccharidosis type VII, and endo-acting heparanase (HPSE), whose overexpression is implicated in inflammation and cancers. The medical importance of these enzymes necessitates reliable methods to assay their activities in tissues. Herein, we present a set of β-glucuronidase-specific activity-based probes (ABPs) that allow rapid and quantitative visualization of GUSB and HPSE in biological samples, providing a powerful tool for dissecting their activities in normal and disease states. Unexpectedly, we find that the supposedly inactive HPSE proenzyme proHPSE is also labeled by our ABPs, leading to surprising insights regarding structural relationships between proHPSE, mature HPSE, and their bacterial homologs. Our results demonstrate the application of β-glucuronidase ABPs in tracking pathologically relevant enzymes and provide a case study of how ABP-driven approaches can lead to discovery of unanticipated structural and biochemical functionality.

PubMed: 28581485
DOI: 10.1038/nchembio.2395

実験手法

X-RAY DIFFRACTION (1.57 Å)