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| | <StructureSection load='6bje' size='340' side='right'caption='[[6bje]], [[Resolution|resolution]] 2.70Å' scene=''> | | <StructureSection load='6bje' size='340' side='right'caption='[[6bje]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6bje]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BJE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BJE FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6bje]] is a 2 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=6BJE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BJE FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PMS:PHENYLMETHANESULFONIC+ACID'>PMS</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LYPLA2, APT2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PMS:PHENYLMETHANESULFONIC+ACID'>PMS</scene></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=6bje FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bje OCA], [http://pdbe.org/6bje PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bje RCSB], [http://www.ebi.ac.uk/pdbsum/6bje PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bje ProSAT]</span></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=6bje FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bje OCA], [https://pdbe.org/6bje PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bje RCSB], [https://www.ebi.ac.uk/pdbsum/6bje PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bje ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/LYPA2_HUMAN LYPA2_HUMAN]] May hydrolyze fatty acids from S-acylated cysteine residues in proteins such as trimeric G alpha proteins or HRAS. Has lysophospholipase activity (By similarity). Deacylates GAP43.<ref>PMID:21152083</ref> | + | [https://www.uniprot.org/uniprot/LYPA2_HUMAN LYPA2_HUMAN] May hydrolyze fatty acids from S-acylated cysteine residues in proteins such as trimeric G alpha proteins or HRAS. Has lysophospholipase activity (By similarity). Deacylates GAP43.<ref>PMID:21152083</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6bje" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6bje" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Thioesterase 3D structures|Thioesterase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Xu, S]] | + | [[Category: Xu S]] |
| - | [[Category: Complex]]
| + | |
| - | [[Category: Inhibitor]]
| + | |
| - | [[Category: Lysophospholipase]]
| + | |
| - | [[Category: Pmsf]]
| + | |
| - | [[Category: Protein binding]]
| + | |
| Structural highlights
Function
LYPA2_HUMAN May hydrolyze fatty acids from S-acylated cysteine residues in proteins such as trimeric G alpha proteins or HRAS. Has lysophospholipase activity (By similarity). Deacylates GAP43.[1]
Publication Abstract from PubMed
Lysophospholipids (LysoPLs) are bioactive lipid species involved in cellular signaling processes and the regulation of cell membrane structure. LysoPLs are metabolized through the action of lysophospholipases, including lysophospholipase A1 (LYPLA1) and lysophospholipase A2 (LYPLA2). A new X-ray crystal structure of LYPLA2 compared with a previously published structure of LYPLA1 demonstrated near-identical folding of the two enzymes; however, LYPLA1 and LYPLA2 have displayed distinct substrate specificities in recombinant enzyme assays. To determine how these in vitro substrate preferences translate into a relevant cellular setting and better understand the enzymes' role in LysoPL metabolism, CRISPR-Cas9 technology was utilized to generate stable KOs of Lypla1 and/or Lypla2 in Neuro2a cells. Using these cellular models in combination with a targeted lipidomics approach, LysoPL levels were quantified and compared between cell lines to determine the effect of losing lysophospholipase activity on lipid metabolism. This work suggests that LYPLA1 and LYPLA2 are each able to account for the loss of the other to maintain lipid homeostasis in cells; however, when both are deleted, LysoPL levels are dramatically increased, causing phenotypic and morphological changes to the cells.
Lysophospholipases cooperate to mediate lipid homeostasis and lysophospholipid signaling.,Wepy JA, Galligan JJ, Kingsley PJ, Xu S, Goodman MC, Tallman KA, Rouzer CA, Marnett LJ J Lipid Res. 2019 Feb;60(2):360-374. doi: 10.1194/jlr.M087890. Epub 2018 Nov 27. PMID:30482805[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Tomatis VM, Trenchi A, Gomez GA, Daniotti JL. Acyl-protein thioesterase 2 catalyzes the deacylation of peripheral membrane-associated GAP-43. PLoS One. 2010 Nov 30;5(11):e15045. doi: 10.1371/journal.pone.0015045. PMID:21152083 doi:http://dx.doi.org/10.1371/journal.pone.0015045
- ↑ Wepy JA, Galligan JJ, Kingsley PJ, Xu S, Goodman MC, Tallman KA, Rouzer CA, Marnett LJ. Lysophospholipases cooperate to mediate lipid homeostasis and lysophospholipid signaling. J Lipid Res. 2019 Feb;60(2):360-374. doi: 10.1194/jlr.M087890. Epub 2018 Nov 27. PMID:30482805 doi:http://dx.doi.org/10.1194/jlr.M087890
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