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| | <StructureSection load='4dpz' size='340' side='right'caption='[[4dpz]], [[Resolution|resolution]] 1.25Å' scene=''> | | <StructureSection load='4dpz' size='340' side='right'caption='[[4dpz]], [[Resolution|resolution]] 1.25Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4dpz]] is a 1 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=4DPZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DPZ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4dpz]] is a 1 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=4DPZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DPZ FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSX:S-OXY+CYSTEINE'>CSX</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CSX:S-OXY+CYSTEINE'>CSX</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4dot|4dot]]</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=4dpz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dpz OCA], [https://pdbe.org/4dpz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dpz RCSB], [https://www.ebi.ac.uk/pdbsum/4dpz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dpz ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HRASLS2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4dpz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dpz OCA], [http://pdbe.org/4dpz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4dpz RCSB], [http://www.ebi.ac.uk/pdbsum/4dpz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4dpz ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/HRSL2_HUMAN HRSL2_HUMAN]] Exhibits PLA1/2 activity, catalyzing the calcium-independent hydrolysis of acyl groups in various phosphatidylcholines (PC) and phosphatidylethanolamine (PE). For most substrates, PLA1 activity is much higher than PLA2 activity. Catalyzes N-acylation of PE using both sn-1 and sn-2 palmitoyl groups of PC as acyl donor. Also catalyzes O-acylation converting lyso-PC into PC.<ref>PMID:19615464</ref> | + | [[https://www.uniprot.org/uniprot/PLAT2_HUMAN PLAT2_HUMAN]] Exhibits both phospholipase A1/2 and acyltransferase activities (PubMed:19615464, PubMed:22825852, PubMed:22605381, PubMed:26503625). Shows phospholipase A1 (PLA1) and A2 (PLA2) activity, catalyzing the calcium-independent release of fatty acids from the sn-1 or sn-2 position of glycerophospholipids (PubMed:19615464, PubMed:22825852, PubMed:22605381). For most substrates, PLA1 activity is much higher than PLA2 activity (PubMed:19615464). Shows O-acyltransferase activity, catalyzing the transfer of a fatty acyl group from glycerophospholipid to the hydroxyl group of lysophospholipid (PubMed:19615464). Shows N-acyltransferase activity, catalyzing the calcium-independent transfer of a fatty acyl group at the sn-1 position of phosphatidylcholine (PC) and other glycerophospholipids to the primary amine of phosphatidylethanolamine (PE), forming N-acylphosphatidylethanolamine (NAPE), which serves as precursor for N-acylethanolamines (NAEs) (PubMed:19615464, PubMed:22825852, PubMed:22605381). Catalyzes N-acylation of PE using both sn-1 and sn-2 palmitoyl groups of PC as acyl donor (PubMed:22605381). Exhibits high phospholipase A1/2 activity and low N-acyltransferase activity (PubMed:22825852).<ref>PMID:19615464</ref> <ref>PMID:22605381</ref> <ref>PMID:22825852</ref> <ref>PMID:26503625</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Golczak, M]] | + | [[Category: Golczak M]] |
| - | [[Category: Kiser, P D]] | + | [[Category: Kiser PD]] |
| - | [[Category: Lodowski, D T]] | + | [[Category: Lodowski DT]] |
| - | [[Category: Palczewski, K]] | + | [[Category: Palczewski K]] |
| - | [[Category: Sears, A E]] | + | [[Category: Sears AE]] |
| - | [[Category: Alpha/beta fold]]
| + | |
| - | [[Category: Enzyme phospholipid acyltransferase]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
[PLAT2_HUMAN] Exhibits both phospholipase A1/2 and acyltransferase activities (PubMed:19615464, PubMed:22825852, PubMed:22605381, PubMed:26503625). Shows phospholipase A1 (PLA1) and A2 (PLA2) activity, catalyzing the calcium-independent release of fatty acids from the sn-1 or sn-2 position of glycerophospholipids (PubMed:19615464, PubMed:22825852, PubMed:22605381). For most substrates, PLA1 activity is much higher than PLA2 activity (PubMed:19615464). Shows O-acyltransferase activity, catalyzing the transfer of a fatty acyl group from glycerophospholipid to the hydroxyl group of lysophospholipid (PubMed:19615464). Shows N-acyltransferase activity, catalyzing the calcium-independent transfer of a fatty acyl group at the sn-1 position of phosphatidylcholine (PC) and other glycerophospholipids to the primary amine of phosphatidylethanolamine (PE), forming N-acylphosphatidylethanolamine (NAPE), which serves as precursor for N-acylethanolamines (NAEs) (PubMed:19615464, PubMed:22825852, PubMed:22605381). Catalyzes N-acylation of PE using both sn-1 and sn-2 palmitoyl groups of PC as acyl donor (PubMed:22605381). Exhibits high phospholipase A1/2 activity and low N-acyltransferase activity (PubMed:22825852).[1] [2] [3] [4]
Publication Abstract from PubMed
Lecithin:retinol acyltransferase-like proteins, also referred to as HRAS-like tumor suppressors, comprise a vertebrate subfamily of papain-like or NlpC/P60 thiol proteases that function as phospholipid-metabolizing enzymes. HRAS-like tumor suppressor 3, a representative member of this group, plays a key role in regulating triglyceride accumulation and energy expenditure in adipocytes and therefore constitutes a novel pharmacological target for treatment of metabolic disorders causing obesity. Here, we delineate a catalytic mechanism common to lecithin:retinol acyltransferase-like proteins and provide evidence for their alternative robust lipid-dependent acyltransferase enzymatic activity. We also determined high resolution crystal structures of HRAS-like tumor suppressor 2 and 3 to gain insight into their active site architecture. Based on this structural analysis, two conformational states of the catalytic Cys-113 were identified that differ in reactivity and thus could define the catalytic properties of these two proteins. Finally, these structures provide a model for the topology of these enzymes and allow identification of the protein-lipid bilayer interface. This study contributes to the enzymatic and structural understanding of HRAS-like tumor suppressor enzymes.
Structural Basis for the Acyltransferase Activity of Lecithin:Retinol Acyltransferase-like Proteins.,Golczak M, Kiser PD, Sears AE, Lodowski DT, Blaner WS, Palczewski K J Biol Chem. 2012 Jul 6;287(28):23790-807. Epub 2012 May 17. PMID:22605381[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Uyama T, Jin XH, Tsuboi K, Tonai T, Ueda N. Characterization of the human tumor suppressors TIG3 and HRASLS2 as phospholipid-metabolizing enzymes. Biochim Biophys Acta. 2009 Dec;1791(12):1114-24. doi:, 10.1016/j.bbalip.2009.07.001. Epub 2009 Jul 14. PMID:19615464 doi:http://dx.doi.org/10.1016/j.bbalip.2009.07.001
- ↑ Golczak M, Kiser PD, Sears AE, Lodowski DT, Blaner WS, Palczewski K. Structural Basis for the Acyltransferase Activity of Lecithin:Retinol Acyltransferase-like Proteins. J Biol Chem. 2012 Jul 6;287(28):23790-807. Epub 2012 May 17. PMID:22605381 doi:10.1074/jbc.M112.361550
- ↑ Uyama T, Ikematsu N, Inoue M, Shinohara N, Jin XH, Tsuboi K, Tonai T, Tokumura A, Ueda N. Generation of N-acylphosphatidylethanolamine by members of the phospholipase A/acyltransferase (PLA/AT) family. J Biol Chem. 2012 Sep 14;287(38):31905-19. doi: 10.1074/jbc.M112.368712. Epub, 2012 Jul 23. PMID:22825852 doi:http://dx.doi.org/10.1074/jbc.M112.368712
- ↑ Mardian EB, Bradley RM, Duncan RE. The HRASLS (PLA/AT) subfamily of enzymes. J Biomed Sci. 2015 Oct 26;22:99. doi: 10.1186/s12929-015-0210-7. PMID:26503625 doi:http://dx.doi.org/10.1186/s12929-015-0210-7
- ↑ Golczak M, Kiser PD, Sears AE, Lodowski DT, Blaner WS, Palczewski K. Structural Basis for the Acyltransferase Activity of Lecithin:Retinol Acyltransferase-like Proteins. J Biol Chem. 2012 Jul 6;287(28):23790-807. Epub 2012 May 17. PMID:22605381 doi:10.1074/jbc.M112.361550
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