5u81
From Proteopedia
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<StructureSection load='5u81' size='340' side='right' caption='[[5u81]], [[Resolution|resolution]] 1.40Å' scene=''> | <StructureSection load='5u81' size='340' side='right' caption='[[5u81]], [[Resolution|resolution]] 1.40Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5u81]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U81 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5U81 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5u81]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Hetga Hetga]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U81 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5U81 FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5u7z|5u7z]], [[5u84|5u84]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5u7z|5u7z]], [[5u84|5u84]]</td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ASAH1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10181 HETGA])</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=5u81 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u81 OCA], [http://pdbe.org/5u81 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5u81 RCSB], [http://www.ebi.ac.uk/pdbsum/5u81 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5u81 ProSAT]</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=5u81 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u81 OCA], [http://pdbe.org/5u81 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5u81 RCSB], [http://www.ebi.ac.uk/pdbsum/5u81 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5u81 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Acid ceramidase (aCDase, ASAH1) hydrolyzes lysosomal membrane ceramide into sphingosine, the backbone of all sphingolipids, to regulate many cellular processes. Abnormal function of aCDase leads to Farber disease, spinal muscular atrophy with progressive myoclonic epilepsy, and is associated with Alzheimer's, diabetes, and cancer. Here, we present crystal structures of mammalian aCDases in both proenzyme and autocleaved forms. In the proenzyme, the catalytic center is buried and protected from solvent. Autocleavage triggers a conformational change exposing a hydrophobic channel leading to the active site. Substrate modeling suggests distinct catalytic mechanisms for substrate hydrolysis versus autocleavage. A hydrophobic surface surrounding the substrate binding channel appears to be a site of membrane attachment where the enzyme accepts substrates facilitated by the accessory protein, saposin-D. Structural mapping of disease mutations reveals that most would destabilize the protein fold. These results will inform the rational design of aCDase inhibitors and recombinant aCDase for disease therapeutics. | ||
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| + | Structural basis for the activation of acid ceramidase.,Gebai A, Gorelik A, Li Z, Illes K, Nagar B Nat Commun. 2018 Apr 24;9(1):1621. doi: 10.1038/s41467-018-03844-2. PMID:29692406<ref>PMID:29692406</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5u81" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Hetga]] | ||
[[Category: Gebai, A]] | [[Category: Gebai, A]] | ||
[[Category: Gorelik, A]] | [[Category: Gorelik, A]] | ||
Revision as of 08:25, 2 May 2018
Acid ceramidase (ASAH1, aCDase) from naked mole rat, Cys143Ala, uncleaved
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Categories: Hetga | Gebai, A | Gorelik, A | Illes, K | Nagar, B | Ceramidase | Ceramide | Hydrolase | Ntn-hydrolase
