5i8r
From Proteopedia
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==aSMase with zinc== | ==aSMase with zinc== | ||
| - | <StructureSection load='5i8r' size='340' side='right' caption='[[5i8r]], [[Resolution|resolution]] 3.65Å' scene=''> | + | <StructureSection load='5i8r' size='340' side='right'caption='[[5i8r]], [[Resolution|resolution]] 3.65Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5i8r]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I8R OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[5i8r]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I8R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5I8R 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=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.646Å</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=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=5i8r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i8r OCA], [https://pdbe.org/5i8r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5i8r RCSB], [https://www.ebi.ac.uk/pdbsum/5i8r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5i8r ProSAT]</span></td></tr> | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | |
</table> | </table> | ||
== Disease == | == Disease == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/ASM_HUMAN ASM_HUMAN] Niemann-Pick disease type A;Niemann-Pick disease type B. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. |
== Function == | == Function == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/ASM_HUMAN ASM_HUMAN] Converts sphingomyelin to ceramide (PubMed:1840600, PubMed:18815062). Also has phospholipase C activities toward 1,2-diacylglycerolphosphocholine and 1,2-diacylglycerolphosphoglycerol.<ref>PMID:1840600</ref> <ref>PMID:18815062</ref> Isoform 2 lacks residues that bind the cofactor Zn(2+) and has no enzyme activity.<ref>PMID:1840600</ref> Isoform 3 lacks residues that bind the cofactor Zn(2+) and has no enzyme activity.<ref>PMID:1840600</ref> |
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Acid sphingomyelinase (ASM) hydrolyzes sphingomyelin to ceramide and phosphocholine, essential components of myelin in neurons. Genetic alterations in ASM lead to ASM deficiency (ASMD) and have been linked to Niemann-Pick disease types A and B. Olipudase alfa, a recombinant form of human ASM, is being developed as enzyme replacement therapy to treat the non-neurological manifestations of ASMD. Here we present the human ASM holoenzyme and product bound structures encompassing all of the functional domains. The catalytic domain has a metallophosphatase fold, and two zinc ions and one reaction product phosphocholine are identified in a histidine-rich active site. The structures reveal the underlying catalytic mechanism, in which two zinc ions activate a water molecule for nucleophilic attack of the phosphodiester bond. Docking of sphingomyelin provides a model that allows insight into the selectivity of the enzyme and how the ASM domains collaborate to complete hydrolysis. Mapping of known mutations provides a basic understanding on correlations between enzyme dysfunction and phenotypes observed in ASMD patients. | ||
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| + | Human acid sphingomyelinase structures provide insight to molecular basis of Niemann-Pick disease.,Zhou YF, Metcalf MC, Garman SC, Edmunds T, Qiu H, Wei RR Nat Commun. 2016 Oct 11;7:13082. doi: 10.1038/ncomms13082. PMID:27725636<ref>PMID:27725636</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5i8r" style="background-color:#fffaf0;"></div> | ||
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| + | ==See Also== | ||
| + | *[[Sphingomyelinase|Sphingomyelinase]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Homo sapiens]] |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Wei RR]] |
| - | [[Category: | + | [[Category: Zhou YF]] |
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Current revision
aSMase with zinc
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