7pm4

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

spinqualitylabelsall models 7pm4, resolution 2.49Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7pm4 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.49Å Ligands: DFU, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease FUCO_HUMAN Fucosidosis. The disease is caused by variants affecting the gene represented in this entry. Function FUCO_HUMAN Alpha-L-fucosidase is responsible for hydrolyzing the alpha-1,6-linked fucose joined to the reducing-end N-acetylglucosamine of the carbohydrate moieties of glycoproteins. Publication Abstract from PubMed Enzymatic hydrolysis of alpha-L-fucose from fucosylated glycoconjugates is consequential in bacterial infections and the neurodegenerative lysosomal storage disorder fucosidosis. Understanding human alpha-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 alpha-L-fucosidase (FucA1) in both an unliganded state and in complex with the inhibitor deoxyfuconojirimycin. These structures, determined at 2.49 A 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. Cryo-EM structures of human fucosidase FucA1 reveal insight into substrate recognition and catalysis.,Armstrong Z, Meek RW, Wu L, Blaza JN, Davies GJ Structure. 2022 Oct 6;30(10):1443-1451.e5. doi: 10.1016/j.str.2022.07.001. Epub , 2022 Jul 29. PMID:35907402 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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