View source for 5hqn


==Catalytic domain of murine Acid Sphingomyelinase (ASMase, ASM, SMPD1)==
<StructureSection load='5hqn' size='340' side='right'caption='[[5hqn]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5hqn]] 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=5HQN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5HQN 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]] 2.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=5hqn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hqn OCA], [https://pdbe.org/5hqn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5hqn RCSB], [https://www.ebi.ac.uk/pdbsum/5hqn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5hqn ProSAT]</span></td></tr>
</table>
== Function ==
[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;">
== 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<ref>PMID:27435900</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5hqn" 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]]