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| | <StructureSection load='5kas' size='340' side='right'caption='[[5kas]], [[Resolution|resolution]] 1.62Å' scene=''> | | <StructureSection load='5kas' size='340' side='right'caption='[[5kas]], [[Resolution|resolution]] 1.62Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5kas]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KAS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KAS FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5kas]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KAS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5KAS 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=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=PC:PHOSPHOCHOLINE'>PC</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]] 1.619Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5kar|5kar]]</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=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=PC:PHOSPHOCHOLINE'>PC</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Smpdl3b, Asml3b ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=5kas FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kas OCA], [https://pdbe.org/5kas PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5kas RCSB], [https://www.ebi.ac.uk/pdbsum/5kas PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5kas ProSAT]</span></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=5kas FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kas OCA], [http://pdbe.org/5kas PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kas RCSB], [http://www.ebi.ac.uk/pdbsum/5kas PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kas ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ASM3B_MOUSE ASM3B_MOUSE]] Lipid-modulating phosphodiesterase. Active on the surface of macrophages and dendritic cells and strongly influences macrophage lipid composition and membrane fluidity. Acts as a negative regulator of Toll-like receptor signaling (PubMed:26095358).<ref>PMID:26095358</ref> | + | [https://www.uniprot.org/uniprot/ASM3B_MOUSE ASM3B_MOUSE] Lipid-modulating phosphodiesterase. Active on the surface of macrophages and dendritic cells and strongly influences macrophage lipid composition and membrane fluidity. Acts as a negative regulator of Toll-like receptor signaling (PubMed:26095358).<ref>PMID:26095358</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Gorelik, A]] | + | [[Category: Gorelik A]] |
| - | [[Category: Heinz, L X]] | + | [[Category: Heinz LX]] |
| - | [[Category: Illes, K]] | + | [[Category: Illes K]] |
| - | [[Category: Nagar, B]] | + | [[Category: Nagar B]] |
| - | [[Category: Superti-Furga, G]] | + | [[Category: Superti-Furga G]] |
| - | [[Category: Extracellular]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Phosphocholine]]
| + | |
| - | [[Category: Phosphoesterase]]
| + | |
| Structural highlights
5kas is a 1 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.619Å |
| Ligands: | , , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
ASM3B_MOUSE Lipid-modulating phosphodiesterase. Active on the surface of macrophages and dendritic cells and strongly influences macrophage lipid composition and membrane fluidity. Acts as a negative regulator of Toll-like receptor signaling (PubMed:26095358).[1]
Publication Abstract from PubMed
The enzyme acid sphingomyelinase-like phosphodiesterase 3B (SMPDL3B) was shown to act as a negative regulator of innate immune signaling, affecting cellular lipid composition and membrane fluidity. Furthermore, several reports identified this enzyme as an off-target of the therapeutic antibody rituximab, with implications in kidney disorders. However, structural information for this protein is lacking. Here we present the high-resolution crystal structure of murine SMPDL3B which reveals a substrate binding site strikingly different from its paralogs. The active site is located in a narrow boot-shaped cavity. We identify a unique loop near the active site which appears to impose size constraints on incoming substrates. A structure in complex with phosphocholine indicates that the protein recognizes this head group via an aromatic box, a typical choline-binding motif. Although a potential substrate for SMPDL3B is sphingomyelin, we identify other possible substrates such as CDP-choline, ATP and ADP. Functional experiments employing structure-guided mutagenesis in macrophages highlight amino acid residues potentially involved in recognition of endogenous substrates. Our study is an important step towards elucidating the specific function of this poorly characterized enzyme.
Crystal Structure of the Acid Sphingomyelinase-Like Phosphodiesterase SMPDL3B Provides Insights into Determinants of Substrate Specificity.,Gorelik A, Heinz LX, Illes K, Superti-Furga G, Nagar B J Biol Chem. 2016 Sep 28. pii: jbc.M116.755801. PMID:27687724[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Heinz LX, Baumann CL, Koberlin MS, Snijder B, Gawish R, Shui G, Sharif O, Aspalter IM, Muller AC, Kandasamy RK, Breitwieser FP, Pichlmair A, Bruckner M, Rebsamen M, Bluml S, Karonitsch T, Fauster A, Colinge J, Bennett KL, Knapp S, Wenk MR, Superti-Furga G. The Lipid-Modifying Enzyme SMPDL3B Negatively Regulates Innate Immunity. Cell Rep. 2015 Jun 30;11(12):1919-28. doi: 10.1016/j.celrep.2015.05.006. Epub, 2015 Jun 18. PMID:26095358 doi:http://dx.doi.org/10.1016/j.celrep.2015.05.006
- ↑ Gorelik A, Heinz LX, Illes K, Superti-Furga G, Nagar B. Crystal Structure of the Acid Sphingomyelinase-Like Phosphodiesterase SMPDL3B Provides Insights into Determinants of Substrate Specificity. J Biol Chem. 2016 Sep 28. pii: jbc.M116.755801. PMID:27687724 doi:http://dx.doi.org/10.1074/jbc.M116.755801
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