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| | <StructureSection load='5fi9' size='340' side='right'caption='[[5fi9]], [[Resolution|resolution]] 2.54Å' scene=''> | | <StructureSection load='5fi9' size='340' side='right'caption='[[5fi9]], [[Resolution|resolution]] 2.54Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5fi9]] is a 2 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=5FI9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5FI9 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5fi9]] is a 2 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=5FI9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5FI9 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=NT8:(1-AZANYL-1-PHOSPHONO-DECYL)PHOSPHONIC+ACID'>NT8</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]] 2.543Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5fib|5fib]], [[5fic|5fic]], [[5hqn|5hqn]]</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=NT8:(1-AZANYL-1-PHOSPHONO-DECYL)PHOSPHONIC+ACID'>NT8</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">Smpd1, Asm ([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=5fi9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fi9 OCA], [https://pdbe.org/5fi9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5fi9 RCSB], [https://www.ebi.ac.uk/pdbsum/5fi9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5fi9 ProSAT]</span></td></tr> |
| - | <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>
| + | |
| - | <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=5fi9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fi9 OCA], [http://pdbe.org/5fi9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fi9 RCSB], [http://www.ebi.ac.uk/pdbsum/5fi9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5fi9 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ASM_MOUSE ASM_MOUSE]] Converts sphingomyelin to ceramide. Also has phospholipase C activities toward 1,2-diacylglycerolphosphocholine and 1,2-diacylglycerolphosphoglycerol.[UniProtKB:P17405] | + | [https://www.uniprot.org/uniprot/ASM_MOUSE ASM_MOUSE] Converts sphingomyelin to ceramide. Also has phospholipase C activities toward 1,2-diacylglycerolphosphocholine and 1,2-diacylglycerolphosphoglycerol.[UniProtKB:P17405] |
| | <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: Sphingomyelin phosphodiesterase]]
| + | [[Category: Gorelik A]] |
| - | [[Category: Gorelik, A]] | + | [[Category: Heinz LX]] |
| - | [[Category: Heinz, L X]] | + | [[Category: Illes K]] |
| - | [[Category: Illes, K]] | + | [[Category: Nagar B]] |
| - | [[Category: Nagar, B]] | + | [[Category: Superti-Furga G]] |
| - | [[Category: Superti-Furga, G]] | + | |
| - | [[Category: Asm]]
| + | |
| - | [[Category: Asmase]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Saposin]]
| + | |
| - | [[Category: Smpd1]]
| + | |
| Structural highlights
5fi9 is a 2 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 2.543Å |
| Ligands: | , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
ASM_MOUSE Converts sphingomyelin to ceramide. Also has phospholipase C activities toward 1,2-diacylglycerolphosphocholine and 1,2-diacylglycerolphosphoglycerol.[UniProtKB:P17405]
Publication Abstract from PubMed
Acid sphingomyelinase (ASMase, ASM, SMPD1) converts sphingomyelin into ceramide, modulating membrane properties and signal transduction. Inactivating mutations in ASMase cause Niemann-Pick disease, and its inhibition is also beneficial in models of depression and cancer. To gain a better understanding of this critical therapeutic target, we determined crystal structures of mammalian ASMase in various conformations. The catalytic domain adopts a calcineurin-like fold with two zinc ions and a hydrophobic track leading to the active site. Strikingly, the membrane interacting saposin domain assumes either a closed globular conformation independent from the catalytic domain, or an open conformation, which establishes an interface with the catalytic domain essential for activity. Structural mapping of Niemann-Pick mutations reveals that most of them likely destabilize the protein's fold. This study sheds light on the molecular mechanism of ASMase function, and provides a platform for the rational development of ASMase inhibitors and therapeutic use of recombinant ASMase.
Crystal structure of mammalian acid sphingomyelinase.,Gorelik A, Illes K, Heinz LX, Superti-Furga G, Nagar B Nat Commun. 2016 Jul 20;7:12196. doi: 10.1038/ncomms12196. PMID:27435900[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Gorelik A, Illes K, Heinz LX, Superti-Furga G, Nagar B. Crystal structure of mammalian acid sphingomyelinase. Nat Commun. 2016 Jul 20;7:12196. doi: 10.1038/ncomms12196. PMID:27435900 doi:http://dx.doi.org/10.1038/ncomms12196
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