8DU5

Murine sialidase-1 (NEU1)

Summary for 8DU5

• Entry DOI: 10.2210/pdb8du5/pdb
• Descriptor: Sialidase-1, alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: sialic acid, sialidase, glycosidase, lysosome, hydrolase
• Biological source: Mus musculus (house mouse)
• Total number of polymer chains: 2
• Total formula weight: 85734.37

Authors

Gorelik, A.,Illes, K.,Nagar, B. (deposition date: 2022-07-26, release date: 2023-05-31, Last modification date: 2023-10-25)

Primary citation

Gorelik, A.,Illes, K.,Mazhab-Jafari, M.T.,Nagar, B.
Structure of the immunoregulatory sialidase NEU1.
Sci Adv, 9:eadf8169-eadf8169, 2023

PubMed Abstract: Sialic 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.

PubMed: 37205763
DOI: 10.1126/sciadv.adf8169

Experimental method

X-RAY DIFFRACTION (3.5 Å)