View source for 3qnt


==NPC1L1 (NTD) Structure==
<StructureSection load='3qnt' size='340' side='right'caption='[[3qnt]], [[Resolution|resolution]] 2.83&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3qnt]] is a 1 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=3QNT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QNT 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]] 2.83&#8491;</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></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=3qnt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qnt OCA], [https://pdbe.org/3qnt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qnt RCSB], [https://www.ebi.ac.uk/pdbsum/3qnt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qnt ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/NPCL1_HUMAN NPCL1_HUMAN] Plays a major role in cholesterol homeostasis. Is critical for the uptake of cholesterol across the plasma membrane of the intestinal enterocyte. Is the direct molecular target of ezetimibe, a drug that inhibits cholesterol absorbtion. Lack of activity leads to multiple lipid transport defects. The protein may have a function in the transport of multiple lipids and their homeostasis, and may play a critical role in regulating lipid metabolism. Acts as a negative regulator of NPC2 and down-regulates its expression and secretion by inhibiting its maturation and accelerating its degradation.<ref>PMID:15928087</ref> <ref>PMID:22095670</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
BACKGROUND: NPC1L1 is the molecular target of the cholesterol lowering drug Ezetimibe and mediates the intestinal absorption of cholesterol. Inhibition or deletion of NPC1L1 reduces intestinal cholesterol absorption, resulting in reduction of plasma cholesterol levels. PRINCIPAL FINDINGS: Here we present the 2.8 A crystal structure of the N-terminal domain (NTD) of NPC1L1 in the absence of cholesterol. The structure, combined with biochemical data, reveals the mechanism of cholesterol selectivity of NPC1L1. Comparison to the cholesterol free and bound structures of NPC1(NTD) reveals that NPC1L1(NTD) is in a closed conformation and the sterol binding pocket is occluded from solvent. CONCLUSION: The structure of NPC1L1(NTD) reveals a degree of flexibility surrounding the entrance to the sterol binding pocket, suggesting a gating mechanism that relies on multiple movements around the entrance to the sterol binding pocket.

The Structure of the NPC1L1 N-Terminal Domain in a Closed Conformation.,Kwon HJ, Palnitkar M, Deisenhofer J PLoS One. 2011 Apr 15;6(4):e18722. PMID:21525977<ref>PMID:21525977</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3qnt" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Kwon HJ]]