6f30

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of ectonucleotide phosphodiesterase/pyrophosphatase-3 (NPP3) in complex with UDPGlcNAc

Structural highlights

6f30 is a 2 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.3Å
Ligands:	, , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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) is a membrane-bound glycoprotein that regulates extracellular levels of nucleotides. NPP3 is known to contribute to the immune response on basophils by hydrolyzing ATP and to regulate the glycosyltransferase activity in Neuro2a cells. Here, we report on crystal structures of the nuclease and phosphodiesterase domains of rat NPP3 in complex with different substrates, products and substrate analogs giving insight into details of the catalytic mechanism. Complex structures with a phosphate ion, the product AMP and the substrate analog AMPNPP provide a consistent picture of the coordination of the substrate in which one zinc ion activates the threonine nucleophile whereas the other zinc ion binds the phosphate group. Co-crystal structures with the dinucleotide substrates Ap4A and UDPGlcNAc reveal a binding pocket for the larger leaving groups of these substrates. The crystal structures as well as mutational and kinetic analysis demonstrate that the larger leaving groups interact only weakly with the enzyme such that the substrate affinity is dominated by the interactions of the first nucleoside group. For this moiety, the nucleobase is stacked between Y290 and F207 and polar interactions with the protein are only formed via water molecules thus explaining the limited nucleobase selectivity.

Crystal structure and substrate binding mode of ectonucleotide phosphodiesterase/pyrophosphatase-3 (NPP3).,Dohler C, Zebisch M, Strater N Sci Rep. 2018 Jul 18;8(1):10874. doi: 10.1038/s41598-018-28814-y. PMID:30022031^[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, Strater N. Crystal structure and substrate binding mode of ectonucleotide phosphodiesterase/pyrophosphatase-3 (NPP3). Sci Rep. 2018 Jul 18;8(1):10874. doi: 10.1038/s41598-018-28814-y. PMID:30022031 doi:http://dx.doi.org/10.1038/s41598-018-28814-y

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6f30"

Categories: Large Structures | Rattus norvegicus | Dohler C | Strater N | Zebisch M

@@ Line 1: / Line 1: @@
 ==Crystal structure of ectonucleotide phosphodiesterase/pyrophosphatase-3 (NPP3) in complex with UDPGlcNAc==
-<StructureSection load='6f30' size='340' side='right' caption='[[6f30]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
+<StructureSection load='6f30' size='340' side='right'caption='[[6f30]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6f30]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6F30 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6F30 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6f30]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6F30 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6F30 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=UD1:URIDINE-DIPHOSPHATE-N-ACETYLGLUCOSAMINE'>UD1</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6f30 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6f30 OCA], [http://pdbe.org/6f30 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6f30 RCSB], [http://www.ebi.ac.uk/pdbsum/6f30 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6f30 ProSAT]</span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=UD1:URIDINE-DIPHOSPHATE-N-ACETYLGLUCOSAMINE'>UD1</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6f30 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6f30 OCA], [https://pdbe.org/6f30 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6f30 RCSB], [https://www.ebi.ac.uk/pdbsum/6f30 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6f30 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/ENPP3_RAT 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]<ref>PMID:9096610</ref>
+[https://www.uniprot.org/uniprot/ENPP3_RAT 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]<ref>PMID:9096610</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 18: / Line 19: @@
 </div>
 <div class="pdbe-citations 6f30" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Ectonucleotide pyrophosphatase/phosphodiesterase 3D structures|Ectonucleotide pyrophosphatase/phosphodiesterase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Dohler, C]]
+[[Category: Large Structures]]
-[[Category: Strater, N]]
+[[Category: Rattus norvegicus]]
-[[Category: Zebisch, M]]
+[[Category: Dohler C]]
-[[Category: Cytosolic protein]]
+[[Category: Strater N]]
-[[Category: Ectonucleotide phosphodiesterase/pyrophosphatase]]
+[[Category: Zebisch M]]
-[[Category: Enzyme]]
-[[Category: Hydrolase]]

6f30

From Proteopedia

Current revision

Crystal structure of ectonucleotide phosphodiesterase/pyrophosphatase-3 (NPP3) in complex with UDPGlcNAc

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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