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| - | [[Image:1gpl.gif|left|200px]]<br /> | |
| - | <applet load="1gpl" size="450" color="white" frame="true" align="right" spinBox="true" | |
| - | caption="1gpl, resolution 2.01Å" /> | |
| - | '''RP2 LIPASE'''<br /> | |
| | | | |
| - | ==Overview== | + | ==RP2 LIPASE== |
| - | We designed chimeric mutants by exchanging the lid domains of the, classical human pancreatic lipase (HPL) and the guinea pig pancreatic, lipase related protein 2 (GPLRP2). This latter enzyme possesses naturally, a large deletion within the lid domain and is not activated by lipid/water, interfaces. Furthermore, GPLRP2 exhibits phospholipase A1 and lipase, activities in the same order of magnitude, whereas HPL has no significant, phospholipase activity and displays a clear interfacial activation. An HPL, mutant [HPL(-lid)] with GPLRP2 mini-lid domain does not display, interfacial activation. Its specific activity toward triglycerides is, however, dramatically reduced. A GPLRP2 mutant [GPLRP2(+lid)] with HPL, full-length lid domain is not interfacially activated, and its lid domain, ... [[http://ispc.weizmann.ac.il/pmbin/getpm?8993339 (full description)]]
| + | <StructureSection load='1gpl' size='340' side='right'caption='[[1gpl]], [[Resolution|resolution]] 2.01Å' scene=''> |
| | + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[1gpl]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Cavia_porcellus Cavia porcellus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GPL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1GPL FirstGlance]. <br> |
| | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.01Å</td></tr> |
| | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</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=1gpl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1gpl OCA], [https://pdbe.org/1gpl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1gpl RCSB], [https://www.ebi.ac.uk/pdbsum/1gpl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1gpl ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/LIPP_HUMAN LIPP_HUMAN] [https://www.uniprot.org/uniprot/LIPR2_CAVPO LIPR2_CAVPO] Lipase that primarily hydrolyzes triglycerides and galactosylglycerides (PubMed:8490016, PubMed:17401110, PubMed:20083229, PubMed:8939760). In neonates, may play a major role in pancreatic digestion of dietary fats such as milk fat globules enriched in long-chain triglycerides (By similarity). Hydrolyzes short-, medium- and long-chain fatty acyls in triglycerides without apparent positional specificity (PubMed:8490016, PubMed:8939760). Can completely deacylate triacylglycerols (By similarity). When the liver matures and bile salt synthesis increases, likely functions mainly as a galactolipase and monoacylglycerol lipase. Hydrolyzes monogalactosyldiglycerols (MGDG) and digalactosyldiacylglycerols (DGDG) present in a plant-based diet, releasing long-chain polyunsaturated fatty acids (PubMed:20083229, PubMed:8939760). Hydrolyzes medium- and long-chain fatty acyls in galactolipids. May act together with LIPF to hydrolyze partially digested triglycerides (By similarity). Hydrolyzes long-chain monoglycerides with high efficiency. In cytotoxic T cells, contributes to perforin-dependent cell lysis, but is unlikely to mediate direct cytotoxicity (By similarity). Also has low phospholipase activity (By similarity). In neurons, required for the localization of the phospholipid 1-oleoyl-2-palmitoyl-PC (OPPC) to neurite tips through acyl chain remodeling of membrane phospholipids (By similarity). The resulting OPPC-rich lipid membrane domain recruits the t-SNARE protein STX4 by selectively interacting with the STX4 transmembrane domain and this promotes surface expression of the dopamine transporter SLC6A3/DAT at neurite tips by facilitating fusion of SLC6A3-containing transport vesicles with the plasma membrane (By similarity).[UniProtKB:P17892][UniProtKB:P54317][UniProtKB:P54318]<ref>PMID:17401110</ref> <ref>PMID:20083229</ref> <ref>PMID:8490016</ref> <ref>PMID:8939760</ref> |
| | + | == Evolutionary Conservation == |
| | + | [[Image:Consurf_key_small.gif|200px|right]] |
| | + | Check<jmol> |
| | + | <jmolCheckbox> |
| | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gp/1gpl_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | + | <text>to colour the structure by Evolutionary Conservation</text> |
| | + | </jmolCheckbox> |
| | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1gpl ConSurf]. |
| | + | <div style="clear:both"></div> |
| | | | |
| - | ==About this Structure== | + | ==See Also== |
| - | 1GPL is a [[http://en.wikipedia.org/wiki/Single_protein Single protein]] structure of sequence from [[http://en.wikipedia.org/wiki/Cavia_porcellus Cavia porcellus]] with CA as [[http://en.wikipedia.org/wiki/ligand ligand]]. Active as [[http://en.wikipedia.org/wiki/Triacylglycerol_lipase Triacylglycerol lipase]], with EC number [[http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.3 3.1.1.3]]. Structure known Active Site: CAT. Full crystallographic information is available from [[http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1GPL OCA]].
| + | *[[Lipase 3D Structures|Lipase 3D Structures]] |
| - | | + | == References == |
| - | ==Reference== | + | <references/> |
| - | Pancreatic lipase structure-function relationships by domain exchange., Carriere F, Thirstrup K, Hjorth S, Ferrato F, Nielsen PF, Withers-Martinez C, Cambillau C, Boel E, Thim L, Verger R, Biochemistry. 1997 Jan 7;36(1):239-48. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=8993339 8993339]
| + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Cavia porcellus]] | | [[Category: Cavia porcellus]] |
| - | [[Category: Single protein]] | + | [[Category: Large Structures]] |
| - | [[Category: Triacylglycerol lipase]]
| + | [[Category: Cambillau C]] |
| - | [[Category: Cambillau, C.]] | + | [[Category: Withers-Martinez C]] |
| - | [[Category: Withers-Martinez, C.]] | + | |
| - | [[Category: CA]]
| + | |
| - | [[Category: chimeric]]
| + | |
| - | [[Category: glycoprotein]]
| + | |
| - | [[Category: hydrolase]]
| + | |
| - | [[Category: lipid degradation]]
| + | |
| - | [[Category: pancreas]]
| + | |
| - | [[Category: serine esterase]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Oct 30 15:16:46 2007''
| + | |
| Structural highlights
Function
LIPP_HUMAN LIPR2_CAVPO Lipase that primarily hydrolyzes triglycerides and galactosylglycerides (PubMed:8490016, PubMed:17401110, PubMed:20083229, PubMed:8939760). In neonates, may play a major role in pancreatic digestion of dietary fats such as milk fat globules enriched in long-chain triglycerides (By similarity). Hydrolyzes short-, medium- and long-chain fatty acyls in triglycerides without apparent positional specificity (PubMed:8490016, PubMed:8939760). Can completely deacylate triacylglycerols (By similarity). When the liver matures and bile salt synthesis increases, likely functions mainly as a galactolipase and monoacylglycerol lipase. Hydrolyzes monogalactosyldiglycerols (MGDG) and digalactosyldiacylglycerols (DGDG) present in a plant-based diet, releasing long-chain polyunsaturated fatty acids (PubMed:20083229, PubMed:8939760). Hydrolyzes medium- and long-chain fatty acyls in galactolipids. May act together with LIPF to hydrolyze partially digested triglycerides (By similarity). Hydrolyzes long-chain monoglycerides with high efficiency. In cytotoxic T cells, contributes to perforin-dependent cell lysis, but is unlikely to mediate direct cytotoxicity (By similarity). Also has low phospholipase activity (By similarity). In neurons, required for the localization of the phospholipid 1-oleoyl-2-palmitoyl-PC (OPPC) to neurite tips through acyl chain remodeling of membrane phospholipids (By similarity). The resulting OPPC-rich lipid membrane domain recruits the t-SNARE protein STX4 by selectively interacting with the STX4 transmembrane domain and this promotes surface expression of the dopamine transporter SLC6A3/DAT at neurite tips by facilitating fusion of SLC6A3-containing transport vesicles with the plasma membrane (By similarity).[UniProtKB:P17892][UniProtKB:P54317][UniProtKB:P54318][1] [2] [3] [4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
See Also
References
- ↑ Eydoux C, De Caro J, Ferrato F, Boullanger P, Lafont D, Laugier R, Carrière F, De Caro A. Further biochemical characterization of human pancreatic lipase-related protein 2 expressed in yeast cells. J Lipid Res. 2007 Jul;48(7):1539-49. PMID:17401110 doi:10.1194/jlr.M600486-JLR200
- ↑ Amara S, Barouh N, Lecomte J, Lafont D, Robert S, Villeneuve P, De Caro A, Carriere F. Lipolysis of natural long chain and synthetic medium chain galactolipids by pancreatic lipase-related protein 2. Biochim Biophys Acta. 2010 Apr;1801(4):508-16. doi: 10.1016/j.bbalip.2010.01.003., Epub 2010 Jan 18. PMID:20083229 doi:http://dx.doi.org/10.1016/j.bbalip.2010.01.003
- ↑ Hjorth A, Carrière F, Cudrey C, Wöldike H, Boel E, Lawson DM, Ferrato F, Cambillau C, Dodson GG, Thim L, et al.. A structural domain (the lid) found in pancreatic lipases is absent in the guinea pig (phospho)lipase. Biochemistry. 1993 May 11;32(18):4702-7. PMID:8490016 doi:10.1021/bi00069a003
- ↑ Withers-Martinez C, Carriere F, Verger R, Bourgeois D, Cambillau C. A pancreatic lipase with a phospholipase A1 activity: crystal structure of a chimeric pancreatic lipase-related protein 2 from guinea pig. Structure. 1996 Nov 15;4(11):1363-74. PMID:8939760
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