5E98

Crystal structure of human heparanase in complex with HepMer M04S02a

5E98 の概要

• エントリーDOI: 10.2210/pdb5e98/pdb
• 関連するPDBエントリー: 5e8m 5e97 5e9b 5e9c
• 分子名称: Heparanase, beta-D-glucopyranuronic acid-(1-4)-2-deoxy-2-(sulfoamino)-alpha-D-glucopyranose-(1-4)-beta-D-glucopyranuronic acid, IMIDAZOLE, ... (8 entities in total)
• 機能のキーワード: glycoside hydrolase, heparan, protein, sugar, 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: 53794.85

構造登録者

Wu, L.,Davies, G.J. (登録日: 2015-10-14, 公開日: 2015-11-18, 最終更新日: 2024-11-13)

主引用文献

Wu, L.,Viola, C.M.,Brzozowski, A.M.,Davies, G.J.
Structural characterization of human heparanase reveals insights into substrate recognition.
Nat.Struct.Mol.Biol., 22:1016-1022, 2015

PubMed Abstract: Heparan sulfate (HS) is a glycosaminoglycan that forms a key component of the extracellular matrix (ECM). Breakdown of HS is carried out by heparanase (HPSE), an endo-β-glucuronidase of the glycoside hydrolase 79 (GH79) family. Overexpression of HPSE results in breakdown of extracellular HS and release of stored growth factors and hence is strongly linked to cancer metastasis. Here we present crystal structures of human HPSE at 1.6-Å to 1.9-Å resolution that reveal how an endo-acting binding cleft is exposed by proteolytic activation of latent proHPSE. We used oligosaccharide complexes to map the substrate-binding and sulfate-recognition motifs. These data shed light on the structure and interactions of a key enzyme involved in ECM maintenance and provide a starting point for the design of HPSE inhibitors for use as biochemical tools and anticancer therapeutics.

PubMed: 26575439
DOI: 10.1038/nsmb.3136

実験手法

X-RAY DIFFRACTION (1.63 Å)