5fi9: Difference between revisions

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-'''Unreleased structure'''
-The entry 5fi9 is ON HOLD  until Paper Publication
+==Closed form of murine Acid Sphingomyelinase in complex with bisphosphonate inhibitor AbPA==
+<StructureSection load='5fi9' size='340' side='right'caption='[[5fi9]], [[Resolution|resolution]] 2.54&Aring;' scene=''>
+== Structural highlights ==
+<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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.543&#8491;</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='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>
+</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.
-Authors: Gorelik, A., Illes, K., Heinz, L.X., Superti-Furga, G., Nagar, B.
+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>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Gorelik, A]]
+<div class="pdbe-citations 5fi9" style="background-color:#fffaf0;"></div>
-[[Category: Illes, K]]
-[[Category: Heinz, L.X]]
+==See Also==
-[[Category: Nagar, B]]
+*[[Sphingomyelinase|Sphingomyelinase]]
-[[Category: Superti-Furga, G]]
+== 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]]