View source for 6ob0


==Compound 2 bound structure of WT Lipoprotein Lipase in Complex with GPIHBP1 Mutant N78D N82D produced in HEK293-F cells==
<StructureSection load='6ob0' size='340' side='right'caption='[[6ob0]], [[Resolution|resolution]] 2.81&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6ob0]] is a 8 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=6OB0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OB0 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]] 2.81&#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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=M3D:2-(3-cyano-4-oxidanyl-phenyl)-~{N}-(2-morpholin-4-ylethyl)benzo[b][1]benzoxepine-5-carboxamide'>M3D</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</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=6ob0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ob0 OCA], [https://pdbe.org/6ob0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ob0 RCSB], [https://www.ebi.ac.uk/pdbsum/6ob0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ob0 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/LIPL_HUMAN LIPL_HUMAN] Hyperlipoproteinemia type 5;Familial lipoprotein lipase deficiency. The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/LIPL_HUMAN LIPL_HUMAN] The primary function of this lipase is the hydrolysis of triglycerides of circulating chylomicrons and very low density lipoproteins (VLDL) (PubMed:27578112). Binding to heparin sulfate proteogylcans at the cell surface is vital to the function. The apolipoprotein, APOC2, acts as a coactivator of LPL activity in the presence of lipids on the luminal surface of vascular endothelium (By similarity).<ref>PMID:11342582</ref> <ref>PMID:27578112</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Lipoprotein lipase (LPL) plays a central role in triglyceride (TG) metabolism. By catalyzing the hydrolysis of TGs present in TG-rich lipoproteins (TRLs), LPL facilitates TG utilization and regulates circulating TG and TRL concentrations. Until very recently, structural information for LPL was limited to homology models, presumably due to the propensity of LPL to unfold and aggregate. By coexpressing LPL with a soluble variant of its accessory protein glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1) and with its chaperone protein lipase maturation factor 1 (LMF1), we obtained a stable and homogenous LPL/GPIHBP1 complex that was suitable for structure determination. We report here X-ray crystal structures of human LPL in complex with human GPIHBP1 at 2.5-3.0 A resolution, including a structure with a novel inhibitor bound to LPL. Binding of the inhibitor resulted in ordering of the LPL lid and lipid-binding regions and thus enabled determination of the first crystal structure of LPL that includes these important regions of the protein. It was assumed for many years that LPL was only active as a homodimer. The structures and additional biochemical data reported here are consistent with a new report that LPL, in complex with GPIHBP1, can be active as a monomeric 1:1 complex. The crystal structures illuminate the structural basis for LPL-mediated TRL lipolysis as well as LPL stabilization and transport by GPIHBP1.

Structure of lipoprotein lipase in complex with GPIHBP1.,Arora R, Nimonkar AV, Baird D, Wang C, Chiu CH, Horton PA, Hanrahan S, Cubbon R, Weldon S, Tschantz WR, Mueller S, Brunner R, Lehr P, Meier P, Ottl J, Voznesensky A, Pandey P, Smith TM, Stojanovic A, Flyer A, Benson TE, Romanowski MJ, Trauger JW Proc Natl Acad Sci U S A. 2019 May 21;116(21):10360-10365. doi:, 10.1073/pnas.1820171116. Epub 2019 May 9. PMID:31072929<ref>PMID:31072929</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6ob0" style="background-color:#fffaf0;"></div>

==See Also==
*[[Lipase 3D Structures|Lipase 3D Structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Arora R]]
[[Category: Benson TE]]
[[Category: Horton PA]]
[[Category: Romanowski MJ]]