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| | ==Crystal structure of human HRASLS3.== | | ==Crystal structure of human HRASLS3.== |
| | <StructureSection load='4dot' size='340' side='right' caption='[[4dot]], [[Resolution|resolution]] 1.96Å' scene=''> | | <StructureSection load='4dot' size='340' side='right' caption='[[4dot]], [[Resolution|resolution]] 1.96Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4dot]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DOT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DOT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4dot]] 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=4DOT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DOT FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PLA2G16, HRASLS3, HREV107 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | + | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PLA2G16, HRASLS3, HREV107 ([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=4dot FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dot OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4dot RCSB], [http://www.ebi.ac.uk/pdbsum/4dot PDBsum]</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=4dot FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dot OCA], [http://pdbe.org/4dot PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4dot RCSB], [http://www.ebi.ac.uk/pdbsum/4dot PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4dot ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PAG16_HUMAN PAG16_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. Specifically catalyzes the release of fatty acids from phospholipids in adipose tissue (By similarity). N- and O-acylation activity is hardly detectable. Might decrease protein phosphatase 2A (PP2A) activity.<ref>PMID:19615464</ref> <ref>PMID:17374643</ref> | + | [[http://www.uniprot.org/uniprot/HRSL3_HUMAN HRSL3_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. Specifically catalyzes the release of fatty acids from phospholipids in adipose tissue (By similarity). N- and O-acylation activity is hardly detectable. Might decrease protein phosphatase 2A (PP2A) activity.<ref>PMID:17374643</ref> <ref>PMID:19615464</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4dot" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==See Also== | | ==See Also== |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Homo sapiens]] | + | [[Category: Human]] |
| | [[Category: Golczak, M]] | | [[Category: Golczak, M]] |
| | [[Category: Kiser, P D]] | | [[Category: Kiser, P D]] |
| Structural highlights
Function
[HRSL3_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. Specifically catalyzes the release of fatty acids from phospholipids in adipose tissue (By similarity). N- and O-acylation activity is hardly detectable. Might decrease protein phosphatase 2A (PP2A) activity.[1] [2]
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[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Nazarenko I, Schafer R, Sers C. Mechanisms of the HRSL3 tumor suppressor function in ovarian carcinoma cells. J Cell Sci. 2007 Apr 15;120(Pt 8):1393-404. Epub 2007 Mar 20. PMID:17374643 doi:http://dx.doi.org/10.1242/jcs.000018
- ↑ 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
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