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-Structure paper
タイトル | Cryo-EM structures of human fucosidase FucA1 reveal insight into substrate recognition and catalysis. |
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ジャーナル・号・ページ | Structure, Vol. 30, Issue 10, Page 1443-11451.e5, Year 2022 |
掲載日 | 2022年10月6日 |
![]() | Zachary Armstrong / Richard W Meek / Liang Wu / James N Blaza / Gideon J Davies / ![]() |
PubMed 要旨 | Enzymatic hydrolysis of α-L-fucose from fucosylated glycoconjugates is consequential in bacterial infections and the neurodegenerative lysosomal storage disorder fucosidosis. Understanding human α- ...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. |
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手法 | EM (単粒子) |
解像度 | 2.49 Å |
構造データ | EMDB-13499, PDB-7pls: EMDB-13520, PDB-7pm4: |
化合物 | ![]() ChemComp-NAG: ![]() ChemComp-HOH: ![]() ChemComp-DFU: |
由来 |
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![]() | HYDROLASE / Fucosidase |