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==Murine acid sphingomyelinase-like phosphodiesterase 3b (SMPDL3B)== | |||
<StructureSection load='5kar' size='340' side='right'caption='[[5kar]], [[Resolution|resolution]] 1.14Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5kar]] 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=5KAR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5KAR FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.142Å</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=GOL:GLYCEROL'>GOL</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=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=5kar FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kar OCA], [https://pdbe.org/5kar PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5kar RCSB], [https://www.ebi.ac.uk/pdbsum/5kar PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5kar ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[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;"> | |||
== 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<ref>PMID:27687724</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5kar" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Sphingomyelinase|Sphingomyelinase]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | |||
[[Category: Gorelik A]] | |||
[[Category: Heinz LX]] | |||
[[Category: Illes K]] | |||
[[Category: Nagar B]] | |||
[[Category: Superti-Furga G]] | |||