7PM4

Cryo-EM structures of human fucosidase FucA1 reveal insight into substate recognition and catalysis.

7PM4 の概要

• エントリーDOI: 10.2210/pdb7pm4/pdb
• EMDBエントリー: 13520
• 分子名称: Tissue alpha-L-fucosidase, 2-acetamido-2-deoxy-beta-D-glucopyranose, (2S,3R,4S,5R)-2-METHYLPIPERIDINE-3,4,5-TRIOL, ... (4 entities in total)
• 機能のキーワード: fucosidase, hydrolase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 203576.02

構造登録者

Armstrong, Z.,Meek, R.W.,Wu, L.,Blaza, J.N.,Davies, G.J. (登録日: 2021-09-01, 公開日: 2022-08-10, 最終更新日: 2024-11-20)

主引用文献

Armstrong, Z.,Meek, R.W.,Wu, L.,Blaza, J.N.,Davies, G.J.
Cryo-EM structures of human fucosidase FucA1 reveal insight into substrate recognition and catalysis.
Structure, 30:1443-, 2022

PubMed Abstract: Enzymatic hydrolysis of α-L-fucose from fucosylated glycoconjugates is consequential in bacterial infections and the neurodegenerative lysosomal storage disorder fucosidosis. Understanding human α-L-fucosidase catalysis, in an effort toward drug design, has been hindered by the absence of three-dimensional structural data for any animal fucosidase. Here, we have used cryoelectron microscopy (cryo-EM) to determine the structure of human lysosomal α-L-fucosidase (FucA1) in both an unliganded state and in complex with the inhibitor deoxyfuconojirimycin. These structures, determined at 2.49 Å resolution, reveal the homotetrameric structure of FucA1, the architecture of the catalytic center, and the location of both natural population variations and disease-causing mutations. Furthermore, this work has conclusively identified the hitherto contentious identity of the catalytic acid/base as aspartate-276, representing a shift from both the canonical glutamate acid/base residue and a previously proposed glutamate residue. These findings have furthered our understanding of how FucA1 functions in both health and disease.

PubMed: 35907402
DOI: 10.1016/j.str.2022.07.001

実験手法

ELECTRON MICROSCOPY (2.49 Å)