View source for 2oxe


==Structure of the Human Pancreatic Lipase-related Protein 2==
<StructureSection load='2oxe' size='340' side='right'caption='[[2oxe]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2oxe]] 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=2OXE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2OXE 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]] 2.8&#8491;</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>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=2oxe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2oxe OCA], [https://pdbe.org/2oxe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2oxe RCSB], [https://www.ebi.ac.uk/pdbsum/2oxe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2oxe ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/LIPR2_HUMAN LIPR2_HUMAN] Lipase with broad substrate specificity. Can hydrolyze both phospholipids and galactolipids. Acts preferentially on monoglycerides, phospholipids and galactolipids. Contributes to milk fat hydrolysis.<ref>PMID:19824014</ref> <ref>PMID:20083229</ref> <ref>PMID:18702514</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/ox/2oxe_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=2oxe ConSurf].
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<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Access to the active site of pancreatic lipase (PL) is controlled by a surface loop, the lid, which normally undergoes conformational changes only upon addition of lipids or amphiphiles. Structures of PL with their lids in the open and functional conformation have required cocrystallization with amphiphiles. Here we report two crystal structures of wild-type and unglycosylated human pancreatic lipase-related protein 2 (HPLRP2) with the lid in an open conformation in the absence of amphiphiles. These structures solved independently are strikingly similar, with some residues of the lid being poorly defined in the electron-density map. The open conformation of the lid is however different from that previously observed in classical liganded PL, suggesting different kinetic properties for HPLRP2. Here we show that the HPLRP2 is directly inhibited by E600, does not present interfacial activation, and acts preferentially on substrates forming monomers or small aggregates (micelles) dispersed in solution like monoglycerides, phospholipids and galactolipids, whereas classical PL displays reverse properties and a high specificity for unsoluble substrates like triglycerides and diglycerides forming oil-in-water interfaces. These biochemical properties imply that the lid of HPLRP2 is likely to spontaneously adopt in solution the open conformation observed in the crystal structure. This open conformation generates a large cavity capable of accommodating the digalactose polar head of galactolipids, similar to that previously observed in the active site of the guinea pig PLRP2, but absent from the classical PL. Most of the structural and kinetic properties of HPLRP2 were found to be different from those of rat PLRP2, the structure of which was previously obtained with the lid in a closed conformation. Our findings illustrate the essential role of the lid in determining the substrate specificity and the mechanism of action of lipases.

Structure of human pancreatic lipase-related protein 2 with the lid in an open conformation.,Eydoux C, Spinelli S, Davis TL, Walker JR, Seitova A, Dhe-Paganon S, De Caro A, Cambillau C, Carriere F Biochemistry. 2008 Sep 9;47(36):9553-64. Epub 2008 Aug 15. PMID:18702514<ref>PMID:18702514</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2oxe" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Arrowsmith CH]]
[[Category: Bochkarev A]]
[[Category: Butler-Cole C]]
[[Category: Davis T]]
[[Category: Dhe-Paganon S]]
[[Category: Edwards AM]]
[[Category: Finerty Jr PJ]]
[[Category: Kozieradzki I]]
[[Category: Seitova A]]
[[Category: Sundstrom M]]
[[Category: Walker JR]]
[[Category: Weigelt J]]