6v3h

Structure of NPC1-like intracellular cholesterol transporter 1 (NPC1L1) in complex with an ezetimibe analogStructure of NPC1-like intracellular cholesterol transporter 1 (NPC1L1) in complex with an ezetimibe analog

Structural highlights

6v3h is a 1 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.5Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

NPCL1_RAT Plays a major role in cholesterol homeostasis (PubMed:17135346). Critical for the uptake of cholesterol across the plasma membrane of the intestinal enterocyte (PubMed:17135346). Involved in plant sterol absorption, it transports sitosterol, although at lower rates than cholesterol (PubMed:17135346). Is the direct molecular target of ezetimibe, a drug that inhibits cholesterol absorption and is approved for the treatment of hypercholesterolemia (PubMed:15928087). May have a function in the transport of multiple lipids and their homeostasis, thereby influencing lipid metabolism regulation (By similarity). May be involved in caveolin trafficking from the plasma membrane (By similarity). Acts as a negative regulator of NPC2 and down-regulates its expression and secretion by inhibiting its maturation and accelerating its degradation (By similarity).[UniProtKB:Q6T3U4][UniProtKB:Q9UHC9]^[1] ^[2]

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, Suzuki H. Niemann-Pick C1-like 1 overexpression facilitates ezetimibe-sensitive cholesterol and beta-sitosterol uptake in CaCo-2 cells. J Pharmacol Exp Ther. 2007 Feb;320(2):559-64. PMID:17135346 doi:10.1124/jpet.106.114181

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OCA

[1] 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

[2] Yamanashi Y, Takada T, Suzuki H. Niemann-Pick C1-like 1 overexpression facilitates ezetimibe-sensitive cholesterol and beta-sitosterol uptake in CaCo-2 cells. J Pharmacol Exp Ther. 2007 Feb;320(2):559-64. PMID:17135346 doi:10.1124/jpet.106.114181

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