5FQL

Insights into Hunter syndrome from the structure of iduronate-2- sulfatase

5FQL の概要

• エントリーDOI: 10.2210/pdb5fql/pdb
• 分子名称: IDURONATE-2-SULFATASE, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• 機能のキーワード: hydrolase, hunter syndrome
• 由来する生物種: HOMO SAPIENS (HUMAN)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 62584.76

構造登録者

Demydchuk, M.,Hill, C.H.,Zhou, A.,Bunkoczi, G.,Stein, P.E.,Marchesan, D.,Deane, J.E.,Read, R.J. (登録日: 2015-12-11, 公開日: 2017-01-18, 最終更新日: 2025-04-09)

主引用文献

Demydchuk, M.,Hill, C.H.,Zhou, A.,Bunkoczi, G.,Stein, P.E.,Marchesan, D.,Deane, J.E.,Read, R.J.
Insights into Hunter syndrome from the structure of iduronate-2-sulfatase.
Nat Commun, 8:15786-15786, 2017

PubMed Abstract: Hunter syndrome is a rare but devastating childhood disease caused by mutations in the IDS gene encoding iduronate-2-sulfatase, a crucial enzyme in the lysosomal degradation pathway of dermatan sulfate and heparan sulfate. These complex glycosaminoglycans have important roles in cell adhesion, growth, proliferation and repair, and their degradation and recycling in the lysosome is essential for cellular maintenance. A variety of disease-causing mutations have been identified throughout the IDS gene. However, understanding the molecular basis of the disease has been impaired by the lack of structural data. Here, we present the crystal structure of human IDS with a covalently bound sulfate ion in the active site. This structure provides essential insight into multiple mechanisms by which pathogenic mutations interfere with enzyme function, and a compelling explanation for severe Hunter syndrome phenotypes. Understanding the structural consequences of disease-associated mutations will facilitate the identification of patients that may benefit from specific tailored therapies.

PubMed: 28593992
DOI: 10.1038/ncomms15786

実験手法

X-RAY DIFFRACTION (2.3 Å)