5tcd

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<StructureSection load='5tcd' size='340' side='right'caption='[[5tcd]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
<StructureSection load='5tcd' size='340' side='right'caption='[[5tcd]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[5tcd]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TCD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TCD FirstGlance]. <br>
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<table><tr><td colspan='2'>[[5tcd]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TCD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5TCD FirstGlance]. <br>
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</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=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PC:PHOSPHOCHOLINE'>PC</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ENPP7, UNQ3077/PRO9912 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<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=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PC:PHOSPHOCHOLINE'>PC</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Sphingomyelin_phosphodiesterase Sphingomyelin phosphodiesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.4.12 3.1.4.12] </span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5tcd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tcd OCA], [https://pdbe.org/5tcd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5tcd RCSB], [https://www.ebi.ac.uk/pdbsum/5tcd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5tcd ProSAT]</span></td></tr>
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<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=5tcd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tcd OCA], [http://pdbe.org/5tcd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tcd RCSB], [http://www.ebi.ac.uk/pdbsum/5tcd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tcd ProSAT]</span></td></tr>
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</table>
</table>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/ENPP7_HUMAN ENPP7_HUMAN]] Converts sphingomyelin to ceramide. Also has phospholipase C activity toward palmitoyl lyso-phosphocholine. Does not appear to have nucleotide pyrophosphatase activity.<ref>PMID:12885774</ref>
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[https://www.uniprot.org/uniprot/ENPP7_HUMAN ENPP7_HUMAN] Converts sphingomyelin to ceramide. Also has phospholipase C activity toward palmitoyl lyso-phosphocholine. Does not appear to have nucleotide pyrophosphatase activity.<ref>PMID:12885774</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Absorption of dietary sphingomyelin (SM) requires its initial degradation into ceramide, a process catalyzed by the intestinal enzyme alkaline sphingomyelinase (alk-SMase, NPP7, ENPP7). Alk-SMase belongs to the nucleotide pyrophosphatase / phosphodiesterase family, the members of which hydrolyze nucleoside phosphates, phospholipids and other related molecules. NPP7 is the only paralog that can cleave SM, and its activity requires the presence of bile salts, a class of physiological anionic detergents. To elucidate the mechanism of substrate recognition, we determined the crystal structure of human alk-SMase in complex with phosphocholine, a reaction product. Although the overall fold and catalytic center is conserved relative to other NPPs, alk-SMase recognizes the choline moiety of its substrates via an NPP7-specific aromatic box composed of tyrosine residues. Mutational analysis and enzymatic activity assays identified features on the surface of the protein - a cationic patch and a unique hydrophobic loop - that are essential for accessing SM in bile salt micelles. These results shed new light on substrate specificity determinants within the NPP enzyme family.
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Crystal Structure of the Human Alkaline Sphingomyelinase Provides Insights into Substrate Recognition.,Gorelik A, Liu F, Illes K, Nagar B J Biol Chem. 2017 Mar 14. pii: jbc.M116.769273. doi: 10.1074/jbc.M116.769273. PMID:28292932<ref>PMID:28292932</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 5tcd" style="background-color:#fffaf0;"></div>
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==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Sphingomyelin phosphodiesterase]]
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[[Category: Gorelik A]]
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[[Category: Gorelik, A]]
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[[Category: Illes K]]
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[[Category: Illes, K]]
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[[Category: Liu F]]
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[[Category: Liu, F]]
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[[Category: Nagar B]]
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[[Category: Nagar, B]]
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[[Category: Glycosylphosphatidylinositol]]
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[[Category: Hydrolase]]
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[[Category: Phosphocholine]]
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[[Category: Sphingomyelin]]
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[[Category: Sphingomyelinase]]
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Revision as of 15:39, 6 March 2024

Human alkaline sphingomyelinase (ENPP7) in complex with phosphocholine

PDB ID 5tcd

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