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4x96

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Revision as of 09:32, 22 November 2017

Low resolution crystal structure of Lecithin:Cholesterol Acyltransferase (LCAT; residues 21-397)

Structural highlights

4x96 is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	4x90, 4x91, 4x92, 4x93, 4x94, 4x95, 4x97
Gene:	LCAT (HUMAN)
Activity:	Phosphatidylcholine--sterol O-acyltransferase, with EC number 2.3.1.43
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[LCAT_HUMAN] Fish-eye disease;Familial LCAT deficiency. 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

[LCAT_HUMAN] Central enzyme in the extracellular metabolism of plasma lipoproteins. Synthesized mainly in the liver and secreted into plasma where it converts cholesterol and phosphatidylcholines (lecithins) to cholesteryl esters and lysophosphatidylcholines on the surface of high and low density lipoproteins (HDLs and LDLs). The cholesterol ester is then transported back to the liver. Has a preference for plasma 16:0-18:2 or 18:O-18:2 phosphatidylcholines. Also produced in the brain by primary astrocytes, and esterifies free cholesterol on nascent APOE-containing lipoproteins secreted from glia and influences cerebral spinal fluid (CSF) APOE- and APOA1 levels. Together with APOE and the cholesterol transporter ABCA1, plays a key role in the maturation of glial-derived, nascent lipoproteins. Required for remodeling high-density lipoprotein particles into their spherical forms.^[1]

Publication Abstract from PubMed

Lysosomal phospholipase A2 (LPLA2) and lecithin:cholesterol acyltransferase (LCAT) belong to a structurally uncharacterized family of key lipid-metabolizing enzymes responsible for lung surfactant catabolism and for reverse cholesterol transport, respectively. Whereas LPLA2 is predicted to underlie the development of drug-induced phospholipidosis, somatic mutations in LCAT cause fish eye disease and familial LCAT deficiency. Here we describe several high-resolution crystal structures of human LPLA2 and a low-resolution structure of LCAT that confirms its close structural relationship to LPLA2. Insertions in the alpha/beta hydrolase core of LPLA2 form domains that are responsible for membrane interaction and binding the acyl chains and head groups of phospholipid substrates. The LCAT structure suggests the molecular basis underlying human disease for most of the known LCAT missense mutations, and paves the way for rational development of new therapeutics to treat LCAT deficiency, atherosclerosis and acute coronary syndrome.

Structure and function of lysosomal phospholipase A2 and lecithin:cholesterol acyltransferase.,Glukhova A, Hinkovska-Galcheva V, Kelly R, Abe A, Shayman JA, Tesmer JJ Nat Commun. 2015 Mar 2;6:6250. doi: 10.1038/ncomms7250. PMID:25727495^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Clay MA, Pyle DH, Rye KA, Barter PJ. Formation of spherical, reconstituted high density lipoproteins containing both apolipoproteins A-I and A-II is mediated by lecithin:cholesterol acyltransferase. J Biol Chem. 2000 Mar 24;275(12):9019-25. PMID:10722751
↑ Glukhova A, Hinkovska-Galcheva V, Kelly R, Abe A, Shayman JA, Tesmer JJ. Structure and function of lysosomal phospholipase A2 and lecithin:cholesterol acyltransferase. Nat Commun. 2015 Mar 2;6:6250. doi: 10.1038/ncomms7250. PMID:25727495 doi:http://dx.doi.org/10.1038/ncomms7250

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4x96"

@@ Line 3: / Line 3: @@
 <StructureSection load='4x96' size='340' side='right' caption='[[4x96]], [[Resolution|resolution]] 8.69&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4x96]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4X96 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4X96 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4x96]] is a 4 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=4X96 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4X96 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4x90|4x90]], [[4x91|4x91]], [[4x92|4x92]], [[4x93|4x93]], [[4x94|4x94]], [[4x95|4x95]], [[4x97|4x97]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LCAT ([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/Phosphatidylcholine--sterol_O-acyltransferase Phosphatidylcholine--sterol O-acyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.43 2.3.1.43] </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=4x96 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x96 OCA], [http://pdbe.org/4x96 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4x96 RCSB], [http://www.ebi.ac.uk/pdbsum/4x96 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4x96 ProSAT]</span></td></tr>
@@ Line 26: / Line 27: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Phosphatidylcholine--sterol O-acyltransferase]]
 [[Category: Glukhova, A]]

4x96

From Proteopedia

Revision as of 09:32, 22 November 2017

Low resolution crystal structure of Lecithin:Cholesterol Acyltransferase (LCAT; residues 21-397)

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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