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PDBsum entry 1olm
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Lipid binding protein
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PDB id
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1olm
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Supernatant protein factor in complex with rrr-Alpha-Tocopherylquinone: a link between oxidized vitamin e and cholesterol biosynthesis.
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Authors
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A.Stocker,
U.Baumann.
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Ref.
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J Mol Biol, 2003,
332,
759-765.
[DOI no: ]
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PubMed id
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Abstract
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The vast majority of monomeric lipid transport in nature is performed by
lipid-specific protein carriers. This class of proteins can enclose cognate
lipid molecules in a hydrophobic cavity and transport them across the aqueous
environment. Supernatant protein factor (SPF) is an enigmatic representative of
monomeric lipid transporters belonging to the SEC14 family. SPF stimulates
squalene epoxidation, a downstream step of the cholesterol biosynthetic pathway,
by an unknown mechanism. Here, we present the three-dimensional crystal
structure of human SPF in complex with RRR-alpha-tocopherylquinone, the major
physiological oxidation product of RRR-alpha-tocopherol, at a resolution of
1.95A. The structure of the complex reveals how SPF sequesters
RRR-alpha-tocopherylquinone (RRR-alpha-TQ) in its protein body and permits a
comparison with the recently solved structure of human alpha-tocopherol transfer
protein (alpha-TTP) in complex with RRR-alpha-tocopherol. Recent findings have
shown that RRR-alpha-TQ is reduced in vivo to RRR-alpha-TQH(2), the latter has
been suggested to protect low-density lipoprotein (LDL) particles from
oxidation. Hence, the antioxidant function of the redox couple
RRR-alpha-TQ/RRR-alpha-TQH(2) in blocking LDL oxidation may reduce cellular
cholesterol uptake and thus explain how SPF upregulates cholesterol synthesis.
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Figure 3.
Figure 3. Stereoview of the SPF-RRR-a-TQ complex in rainbow
coloring from blue (N terminus) to red (C terminus) showing the
three-helix coil in dark blue, CRAL_TRIO lipid-binding domain in
light blue and green, jelly-roll in yellow and red, cavity in
gray (for details see Figure 5), lipid-exchange loop in pink and
RRR-a-TQ in black.
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Figure 5.
Figure 5. Stereoview of the ligand-binding pockets of: A,
SPF with RRR-a-TQ; and B, a-TTP with RRR-a-T. Cavities are shown
after least-squares superimposition of the C^a traces of the
protein structures. Ligands are shown in black; side-chains in
gray; oxygen, nitrogen and sulfur atoms in red, blue and orange,
respectively; cavities in light gray. Cavities were calculated
with the program VOIDOO.[30.]
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2003,
332,
759-765)
copyright 2003.
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