8du5
Murine sialidase-1 (NEU1)
Structural highlights
FunctionNEUR1_MOUSE Catalyzes the removal of sialic acid (N-acetylneuraminic acid) moieties from glycoproteins and glycolipids. To be active, it is strictly dependent on its presence in the multienzyme complex. Appears to have a preference for alpha 2-3 and alpha 2-6 sialyl linkage.[1] [2] Publication Abstract from PubMedSialic acids linked to glycoproteins and glycolipids are important mediators of cell and protein recognition events. These sugar residues are removed by neuraminidases (sialidases). Neuraminidase-1 (sialidase-1 or NEU1) is a ubiquitously expressed mammalian sialidase located in lysosomes and on the cell membrane. Because of its modulation of multiple signaling processes, it is a potential therapeutic target for cancers and immune disorders. Genetic defects in NEU1 or in its protective protein cathepsin A (PPCA, CTSA) cause the lysosomal storage diseases sialidosis and galactosialidosis. To further our understanding of this enzyme's function at the molecular level, we determined the three-dimensional structure of murine NEU1. The enzyme oligomerizes through two self-association interfaces and displays a wide substrate-binding cavity. A catalytic loop adopts an inactive conformation. We propose a mechanism of activation involving a conformational change in this loop upon binding to its protective protein. These findings may facilitate the development of selective inhibitor and agonist therapies. Structure of the immunoregulatory sialidase NEU1.,Gorelik A, Illes K, Mazhab-Jafari MT, Nagar B Sci Adv. 2023 May 19;9(20):eadf8169. doi: 10.1126/sciadv.adf8169. Epub 2023 May , 19. PMID:37205763[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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