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3qnt

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Revision as of 03:34, 25 December 2014

NPC1L1 (NTD) Structure

Structural highlights

3qnt is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	NPC1L1 (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[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.^[1] ^[2]

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^[3]

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

References

↑ Garcia-Calvo M, Lisnock J, Bull HG, Hawes BE, Burnett DA, Braun MP, Crona JH, Davis HR Jr, Dean DC, Detmers PA, Graziano MP, Hughes M, Macintyre DE, Ogawa A, O'neill KA, Iyer SP, Shevell DE, Smith MM, Tang YS, Makarewicz AM, Ujjainwalla F, Altmann SW, Chapman KT, Thornberry NA. The target of ezetimibe is Niemann-Pick C1-Like 1 (NPC1L1). Proc Natl Acad Sci U S A. 2005 Jun 7;102(23):8132-7. Epub 2005 May 31. PMID:15928087 doi:10.1073/pnas.0500269102
↑ Yamanashi Y, Takada T, Shoda J, Suzuki H. Novel function of Niemann-Pick C1-like 1 as a negative regulator of Niemann-Pick C2 protein. Hepatology. 2012 Mar;55(3):953-64. doi: 10.1002/hep.24772. Epub 2012 Jan 30. PMID:22095670 doi:10.1002/hep.24772
↑ Kwon HJ, Palnitkar M, Deisenhofer J. The Structure of the NPC1L1 N-Terminal Domain in a Closed Conformation. PLoS One. 2011 Apr 15;6(4):e18722. PMID:21525977 doi:10.1371/journal.pone.0018722

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3qnt"

Categories: Homo sapiens | Kwon, H J | Cholesterol transport protein | Transport protein

@@ Line 7: / Line 7: @@
 <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=3qnt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qnt OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3qnt RCSB], [http://www.ebi.ac.uk/pdbsum/3qnt PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://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 ==

3qnt

From Proteopedia

Revision as of 03:34, 25 December 2014

NPC1L1 (NTD) Structure

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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