4UZ1
STRUCTURE OF THE WNT DEACYLASE NOTUM - CRYSTAL FORM III - 1.4A
Summary for 4UZ1
| Entry DOI | 10.2210/pdb4uz1/pdb |
| Related | 4UYU 4UYW 4UYZ 4UZ5 4UZ6 4UZ7 4UZ9 4UZA 4UZJ 4UZK 4UZL 4UZQ 4WBH |
| Descriptor | NOTUM, 2-acetamido-2-deoxy-beta-D-glucopyranose, SULFATE ION, ... (4 entities in total) |
| Functional Keywords | hydrolase, esterase, extracellular, alpha/beta hydrolase |
| Biological source | HOMO SAPIENS (HUMAN) |
| Cellular location | Secreted : Q6P988 |
| Total number of polymer chains | 1 |
| Total formula weight | 44172.61 |
| Authors | Zebisch, M.,Jones, E.Y. (deposition date: 2014-09-04, release date: 2015-02-25, Last modification date: 2024-10-23) |
| Primary citation | Kakugawa, S.,Langton, P.F.,Zebisch, M.,Howell, S.A.,Chang, T.,Liu, Y.,Feizi, T.,Bineva, G.,O'Reilly, N.,Snijders, A.P.,Jones, E.Y.,Vincent, J. Notum Deacylates Wnt Proteins to Suppress Signalling Activity. Nature, 519:187-, 2015 Cited by PubMed Abstract: Signalling by Wnt proteins is finely balanced to ensure normal development and tissue homeostasis while avoiding diseases such as cancer. This is achieved in part by Notum, a highly conserved secreted feedback antagonist. Notum has been thought to act as a phospholipase, shedding glypicans and associated Wnt proteins from the cell surface. However, this view fails to explain specificity, as glypicans bind many extracellular ligands. Here we provide genetic evidence in Drosophila that Notum requires glypicans to suppress Wnt signalling, but does not cleave their glycophosphatidylinositol anchor. Structural analyses reveal glycosaminoglycan binding sites on Notum, which probably help Notum to co-localize with Wnt proteins. They also identify, at the active site of human and Drosophila Notum, a large hydrophobic pocket that accommodates palmitoleate. Kinetic and mass spectrometric analyses of human proteins show that Notum is a carboxylesterase that removes an essential palmitoleate moiety from Wnt proteins and thus constitutes the first known extracellular protein deacylase. PubMed: 25731175DOI: 10.1038/NATURE14259 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.4 Å) |
Structure validation
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