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 Cited by 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: 35907402DOI: 10.1016/j.str.2022.07.001 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.49 Å) |
Structure validation
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