Structural highlights
Function
[ENPP3_RAT] Hydrolase that metabolizes extracellular nucleotides, including ATP, GTP, UTP and CTP (By similarity). Limits mast cell and basophil responses during inflammation and during the chronic phases of allergic responses by eliminating the extracellular ATP that functions as signaling molecule and activates basophils and mast cells and induces the release of inflammatory cytokines. Metabolizes extracellular ATP in the lumen of the small intestine, and thereby prevents ATP-induced apoptosis of intestinal plasmacytoid dendritic cells (By similarity). Has also alkaline phosphodiesterase activity (PubMed:9096610).[UniProtKB:O14638][UniProtKB:Q6DYE8][1]
Publication Abstract from PubMed
Ectonucleotide phosphodiesterase/pyrophosphatase-3 (NPP3, ENPP3) is an ATP-hydrolyzing glycoprotein that is located in the extracellular space. The full-length ectodomain of rat NPP3 was expressed in HEK293S GntI(-) cells, purified using two chromatographic steps and crystallized. Its structure at 2.77 A resolution reveals that the active-site zinc ions are missing and a large part of the active site and the surrounding residues are flexible. The SMB-like domains have the same orientation in all four molecules in the asymmetric unit. The SMB2 domain is oriented as in NPP2, but the SMB1 domain does not interact with the PDE domain but extends further away from the PDE domain. Deletion of the SMB domains resulted in crystals that diffracted to 2.4 A resolution and are suitable for substrate-binding studies.
Crystallization of ectonucleotide phosphodiesterase/pyrophosphatase-3 and orientation of the SMB domains in the full-length ectodomain.,Dohler C, Zebisch M, Krinke D, Robitzki A, Strater N Acta Crystallogr F Struct Biol Commun. 2018 Nov 1;74(Pt 11):696-703. doi:, 10.1107/S2053230X18011111. Epub 2018 Oct 16. PMID:30387774[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Scott LJ, Delautier D, Meerson NR, Trugnan G, Goding JW, Maurice M. Biochemical and molecular identification of distinct forms of alkaline phosphodiesterase I expressed on the apical and basolateral plasma membrane surfaces of rat hepatocytes. Hepatology. 1997 Apr;25(4):995-1002. PMID:9096610 doi:http://dx.doi.org/S0270913997001924
- ↑ Dohler C, Zebisch M, Krinke D, Robitzki A, Strater N. Crystallization of ectonucleotide phosphodiesterase/pyrophosphatase-3 and orientation of the SMB domains in the full-length ectodomain. Acta Crystallogr F Struct Biol Commun. 2018 Nov 1;74(Pt 11):696-703. doi:, 10.1107/S2053230X18011111. Epub 2018 Oct 16. PMID:30387774 doi:http://dx.doi.org/10.1107/S2053230X18011111
