View source for 5fib


==Open form of murine Acid Sphingomyelinase==
<StructureSection load='5fib' size='340' side='right' caption='[[5fib]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5fib]] 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=5FIB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5FIB 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=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5fi9|5fi9]], [[5fic|5fic]], [[5hqn|5hqn]]</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='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=5fib FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fib OCA], [http://pdbe.org/5fib PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fib RCSB], [http://www.ebi.ac.uk/pdbsum/5fib PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5fib ProSAT]</span></td></tr>
</table>
== 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] 
<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 5fib" style="background-color:#fffaf0;"></div>

==See Also==
*[[Sphingomyelinase|Sphingomyelinase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Lk3 transgenic mice]]
[[Category: Sphingomyelin phosphodiesterase]]
[[Category: Gorelik, A]]
[[Category: Heinz, L X]]
[[Category: Illes, K]]
[[Category: Nagar, B]]
[[Category: Superti-Furga, G]]
[[Category: Asm]]
[[Category: Asmase]]
[[Category: Hydrolase]]
[[Category: Saposin]]
[[Category: Smpd1]]