5fc5: Difference between revisions
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<StructureSection load='5fc5' size='340' side='right'caption='[[5fc5]], [[Resolution|resolution]] 1.68Å' scene=''> | <StructureSection load='5fc5' size='340' side='right'caption='[[5fc5]], [[Resolution|resolution]] 1.68Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5fc5]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[5fc5]] is a 1 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=5FC5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5FC5 FirstGlance]. <br> | ||
</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=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=PC:PHOSPHOCHOLINE'>PC</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]] 1.678Å</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=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=PC:PHOSPHOCHOLINE'>PC</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=5fc5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fc5 OCA], [https://pdbe.org/5fc5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5fc5 RCSB], [https://www.ebi.ac.uk/pdbsum/5fc5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5fc5 ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/ASM3A_MOUSE ASM3A_MOUSE] | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Mus musculus]] | ||
[[Category: Gorelik | [[Category: Gorelik A]] | ||
[[Category: Illes | [[Category: Illes K]] | ||
[[Category: Nagar | [[Category: Nagar B]] | ||
[[Category: Superti-Furga | [[Category: Superti-Furga G]] | ||
Latest revision as of 09:45, 19 July 2023
Murine SMPDL3A in complex with phosphocholineMurine SMPDL3A in complex with phosphocholine
Structural highlights
FunctionPublication Abstract from PubMedSphingomyelin phosphodiesterase, acid-like 3A (SMPDL3A) is a member of a small family of proteins founded by the well-characterized lysosomal enzyme, acid sphingomyelinase (ASM, ASMase). ASMase converts sphingomyelin (SM) into the signaling lipid, ceramide. It was recently discovered that, in contrast to ASMase, SMPDL3A is inactive against SM and, surprisingly, can instead hydrolyze nucleoside diphosphates and triphosphates, which may play a role in purinergic signaling. As none of the ASMase-like proteins have been structurally characterized to date, the molecular basis for their substrate preferences are unknown. Here we report crystal structures of murine SMPDL3A, which represent the first structures of an ASMase-like protein. The catalytic domain consists of a central mixed beta-sandwich surrounded by alpha-helices. Additionally, SMPDL3A possesses a unique C-terminal domain formed from a cluster of four alpha-helices that appears to distinguish this protein family from other phosphoesterases. We show that SMDPL3A is a di-zinc-dependent enzyme with an active site configuration that suggests a mechanism of phosphodiester hydrolysis by a metal-activated water molecule and protonation of the leaving group by a histidine residue. Co-crystal structures of SMPDL3A with AMP and alpha,beta-methylene ADP (AMPCP) reveal that the substrate binding site accommodates nucleotides by establishing interactions with their base, sugar and phosphate moieties, with the latter being the major contributor to binding affinity. Our study provides the structural basis for SMPDL3A substrate specificity and sheds new light on the function of ASMase-like proteins. Structural Basis for Nucleotide Hydrolysis by the Acid Sphingomyelinase-Like Phosphodiesterase SMPDL3A.,Gorelik A, Illes K, Superti-Furga G, Nagar B J Biol Chem. 2016 Jan 20. pii: jbc.M115.711085. PMID:26792860[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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