6v7n
From Proteopedia
(Difference between revisions)
| Line 1: | Line 1: | ||
==Crystal Structure of a human Lysosome Resident Glycoprotein, Lysosomal Acid Lipase, and its Implications in Cholesteryl Ester Storage Disease (CESD)== | ==Crystal Structure of a human Lysosome Resident Glycoprotein, Lysosomal Acid Lipase, and its Implications in Cholesteryl Ester Storage Disease (CESD)== | ||
| - | <StructureSection load='6v7n' size='340' side='right'caption='[[6v7n]]' scene=''> | + | <StructureSection load='6v7n' size='340' side='right'caption='[[6v7n]], [[Resolution|resolution]] 2.62Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6V7N OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6V7N FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6v7n]] is a 2 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=6V7N OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6V7N FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6v7n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v7n OCA], [http://pdbe.org/6v7n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6v7n RCSB], [http://www.ebi.ac.uk/pdbsum/6v7n PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6v7n ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LIPA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Sterol_esterase Sterol esterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.13 3.1.1.13] </span></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6v7n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v7n OCA], [http://pdbe.org/6v7n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6v7n RCSB], [http://www.ebi.ac.uk/pdbsum/6v7n PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6v7n ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Disease == | ||
| + | [[http://www.uniprot.org/uniprot/LICH_HUMAN LICH_HUMAN]] NON RARE IN EUROPE: Heterozygous familial hypercholesterolemia;Cholesteryl ester storage disease;Wolman disease. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/LICH_HUMAN LICH_HUMAN]] Catalyzes the deacylation of triacylglyceryl and cholesteryl ester core lipids of endocytosed low density lipoproteins to generate free fatty acids and cholesterol.<ref>PMID:15269241</ref> <ref>PMID:1718995</ref> <ref>PMID:7204383</ref> <ref>PMID:8112342</ref> <ref>PMID:9633819</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Lysosomal acid lipase (LAL) is a serine hydrolase which hydrolyzes cholesteryl ester and triglycerides delivered to the lysosomes into free cholesterol and fatty acids. LAL deficiency due to mutations in the LAL gene (LIPA) results in accumulation of triglycerides and cholesterol esters in various tissues of the body leading to pathological conditions such as Wolman's disease (WD) and Cholesteryl ester storage disease (CESD). Here we present the first crystal structure of recombinant human LAL to 2.6 A resolution in its closed form. The crystal structure was enabled by mutating three of the six potential glycosylation sites. The overall structure of human LAL (HLAL) closely resembles that of the evolutionarily related human gastric lipase (HGL). It consists of a core domain belonging to the classical alpha/beta hydrolase-fold family with a classical catalytic triad (Ser-153, His-353, Asp-324), an oxyanion hole and a "cap" domain, which regulates substrate entry to the catalytic site. Most significant structural differences between HLAL and HGL exist at the lid region. Deletion of the short helix, 238NLCFLLC244, at the lid region implied a possible role in regulating the highly hydrophobic substrate binding site from self-oligomerization during interfacial activation. We also performed molecular dynamic simulations of dog gastric lipase (DGL), lid open form and HLAL to gain insights and speculated a possible role of the human mutant, H274Y, leading to CESD. | ||
| + | |||
| + | Crystal Structure of human Lysosomal Acid Lipase and its Implications in Cholesteryl Ester Storage Disease (CESD).,Rajamohan F, Reyes AR, Tu M, Nedoma NL, Hoth LR, Schwaid AG, Kurumbail RG, Ward J, Han S J Lipid Res. 2020 Jun 1. pii: jlr.RA120000748. doi: 10.1194/jlr.RA120000748. PMID:32482718<ref>PMID:32482718</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6v7n" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Han S]] | + | [[Category: Sterol esterase]] |
| + | [[Category: Han, S]] | ||
| + | [[Category: Cholesteryl ester storage disease]] | ||
| + | [[Category: Hydrolase]] | ||
| + | [[Category: Lysosomal acid lipase]] | ||
Revision as of 10:03, 12 August 2020
Crystal Structure of a human Lysosome Resident Glycoprotein, Lysosomal Acid Lipase, and its Implications in Cholesteryl Ester Storage Disease (CESD)
| |||||||||||
