7RG8

Crystal Structure of a Stable Heparanase Mutant

7RG8 の概要

• エントリーDOI: 10.2210/pdb7rg8/pdb
• 分子名称: Heparanase 50 kDa subunit, Heparanase 8 kDa subunit, ACETATE ION, ... (5 entities in total)
• 機能のキーワード: heparanase, heparan sulfate, 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: 53794.41

構造登録者

Whitefield, C.,Hong, N.S.,Jackson, C.J. (登録日: 2021-07-14, 公開日: 2022-03-02, 最終更新日: 2024-10-30)

主引用文献

Whitefield, C.,Hong, N.,Mitchell, J.A.,Jackson, C.J.
Computational design and experimental characterisation of a stable human heparanase variant.
Rsc Chem Biol, 3:341-349, 2022

PubMed Abstract: Heparanase is the only human enzyme known to hydrolyse heparin sulfate and is involved in many important physiological processes. However, it is also unregulated in many disease states, such as cancer, diabetes and Covid-19. It is thus an important drug target, yet the heterologous production of heparanase is challenging and only possible in mammalian or insect expression systems, which limits the ability of many laboratories to study it. Here we describe the computational redesign of heparanase to allow high yield expression in . This mutated form of heparanase exhibits essentially identical kinetics, inhibition, structure and protein dynamics to the wild type protein, despite the presence of 26 mutations. This variant will facilitate wider study of this important enzyme and contributes to a growing body of literature that shows evolutionarily conserved and functionally neutral mutations can have significant effects on protein folding and expression.

PubMed: 35382258
DOI: 10.1039/d1cb00239b

実験手法

X-RAY DIFFRACTION (1.3 Å)