7PM4

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

Summary for 7PM4

• Entry DOI: 10.2210/pdb7pm4/pdb
• EMDB information: 13520
• Descriptor: 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)
• Functional Keywords: fucosidase, hydrolase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 4
• Total formula weight: 203576.02

Authors

Armstrong, Z.,Meek, R.W.,Wu, L.,Blaza, J.N.,Davies, G.J. (deposition date: 2021-09-01, release date: 2022-08-10, Last modification date: 2024-11-20)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (2.49 Å)