9GTC

Crystal structure of human lysosomal acid-alpha-glucosidase, GAA, in complex with iminosugar compound 4g

これはPDB形式変換不可エントリーです。

9GTC の概要

• エントリーDOI: 10.2210/pdb9gtc/pdb
• 関連するPDBエントリー: 9GSV 9GSW
• 分子名称: Lysosomal alpha-glucosidase, 1,2-ETHANEDIOL, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (11 entities in total)
• 機能のキーワード: acid-alpha-glucosidase, lysosomal, iminosugar, pompe disease, hydrolase
• 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: 110138.77

構造登録者

Sulzenbacher, G.,Roig-Zamboni, V.,Moracci, M.,Parenti, G.,Py, S. (登録日: 2024-09-17, 公開日: 2025-10-01, 最終更新日: 2025-10-08)

主引用文献

Vieira Da Cruz, A.,Perraudin, V.,Minopoli, N.,Iacono, R.,Roig-Zamboni, V.,Bossio, A.,Tangara, S.,Fayolle, M.,Kanazawa, A.,Philouze, C.,Tarallo, A.,Heming, J.J.A.,Artola, M.,Behr, J.B.,Overkleeft, H.S.,Moracci, M.,Sulzenbacher, G.,Parenti, G.,Py, S.
C -Branched Iminosugars as Selective Pharmacological Chaperones of Lysosomal alpha-Glucosidase for the Treatment of Pompe Disease.
J.Med.Chem., 68:19269-19286, 2025

PubMed Abstract: We report herein the design and synthesis of a series of 5--alkyldeoxynojirimycins from l-sorbose, through an efficient and scalable method amenable to preparing a large variety of analogues. The interaction of this class of compounds with human acid α-glucosidase (GAA), the genetically defective enzyme in patients suffering from Pompe disease, was investigated to identify pharmacological chaperones exhibiting high selectivity for this enzyme. Crystallographic analyses provided a rationale for their binding mode to GAA and chaperone activity. The effects of 5--phenethyl-DNJ () were evaluated on GAA activity enhancement in cells from Pompe disease patients and in GAA-KO mice. The significant increase of GAA activity in the presence of in various tissues, particularly in the diaphragm, encourages further studies on this class of small molecules toward developing clinical drugs. Their chaperone activity and excellent selectivity may offer potential benefits over the current treatments for Pompe disease.

PubMed: 40951993
DOI: 10.1021/acs.jmedchem.5c01349

実験手法

X-RAY DIFFRACTION (2.58 Å)