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PDBsum entry 4omj
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Transport protein
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PDB id
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4omj
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PDB id:
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| Name: |
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Transport protein
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Title:
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Crystal structure of spf bound to 2,3-oxidosqualene
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Structure:
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Sec14-like protein 2. Chain: a, b. Fragment: unp residues 1-275. Synonym: alpha-tocopherol-associated protein, tap, htap, squalene transfer protein, supernatant protein factor, spf. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: c22orf6, kiaa1186, kiaa1658, sec14l2. Expressed in: escherichia coli. Expression_system_taxid: 562.
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Resolution:
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1.60Å
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R-factor:
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0.156
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R-free:
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0.179
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Authors:
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M.Christen,M.J.Marcaida,C.Lamprakis,M.Cascella,A.Stocker
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Key ref:
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M.Christen
et al.
(2015).
Structural insights on cholesterol endosynthesis: Binding of squalene and 2,3-oxidosqualene to supernatant protein factor.
J Struct Biol,
190,
261-270.
PubMed id:
DOI:
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Date:
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27-Jan-14
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Release date:
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15-Apr-15
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PROCHECK
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Headers
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References
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O76054
(S14L2_HUMAN) -
SEC14-like protein 2 from Homo sapiens
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Seq:
Struc:
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403 a.a.
274 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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DOI no:
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J Struct Biol
190:261-270
(2015)
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PubMed id:
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Structural insights on cholesterol endosynthesis: Binding of squalene and 2,3-oxidosqualene to supernatant protein factor.
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M.Christen,
M.J.Marcaida,
C.Lamprakis,
W.Aeschimann,
J.Vaithilingam,
P.Schneider,
M.Hilbert,
G.Schneider,
M.Cascella,
A.Stocker.
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ABSTRACT
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We present the crystal structures of the SEC14-like domain of supernatant
protein factor (SPF) in complex with squalene and 2,3-oxidosqualene. The
structures were resolved at 1.75Å (complex with squalene) and 1.6Å resolution
(complex with 2,3-oxidosqualene), leading in both cases to clear images of the
protein/substrate interactions. Ligand binding is facilitated by removal of the
Golgi-dynamics (GOLD) C-terminal domain of SPF, which, as shown in previous
structures of the apo-protein, blocked the opening of the binding pocket to the
exterior. Both substrates bind into a large hydrophobic cavity, typical of such
lipid-transporter family. Our structures report no specific recognition mode for
the epoxide group. In fact, for both molecules, ligand affinity is dominated by
hydrophobic interactions, and independent investigations by computational models
or differential scanning micro-calorimetry reveal similar binding affinities for
both ligands. Our findings elucidate the molecular bases of the role of SPF in
sterol endo-synthesis, supporting the original hypothesis that SPF is a
facilitator of substrate flow within the sterol synthetic pathway. Moreover, our
results suggest that the GOLD domain acts as a regulator, as its conformational
displacement must occur to favor ligand binding and release during the different
synthetic steps.
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Links
