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PDBsum entry 1cbs
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Retinoic-acid transport
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PDB id
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1cbs
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References listed in PDB file
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Key reference
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Title
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Crystal structures of cellular retinoic acid binding proteins i and ii in complex with all-Trans-Retinoic acid and a synthetic retinoid.
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Authors
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G.J.Kleywegt,
T.Bergfors,
H.Senn,
P.Le motte,
B.Gsell,
K.Shudo,
T.A.Jones.
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Ref.
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Structure, 1994,
2,
1241-1258.
[DOI no: ]
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PubMed id
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Abstract
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BACKGROUND: Retinoic acid (RA) plays a fundamental role in diverse cellular
activities. Cellular RA binding proteins (CRABPs) are thought to act by
modulating the amount of RA available to nuclear RA receptors. CRABPs and
cellular retinol-binding proteins (CRBPs) share a unique fold of two orthogonal
beta-sheets that encapsulate their ligands. It has been suggested that a trio of
residues are the prime determinants defining the high specificity of CRBPs and
CRABPs for their physiological ligands. RESULTS: Bovine/murine CRABP I and human
CRABP II have been crystallized in complex with their natural ligand,
all-trans-RA. Human CRABP II has also been crystallized in complex with a
synthetic retinoid, 'compound 19'. Their structures have been determined and
refined at resolutions of 2.9 A, 1.8 A and 2.2 A, respectively. CONCLUSIONS: The
retinoid-binding site in CRABPs differs significantly from that observed in
CRBP. Structural changes in three juxtaposed areas of the protein create a new,
displaced binding site for RA. The carboxylate of the ligand interacts with the
expected trio of residues (Arg132, Tyr134 and Arg111; CRABP II numbering). The
RA ligand is almost flat with the beta-ionone ring showing a significant
deviation (-33 degrees) from a cis conformation relative to the isoprene tail.
The edge atoms of the beta-ionone ring are accessible to solvent in a suitable
orientation for presentation to metabolizing enzymes. The bulkier synthetic
retinoid causes small conformational changes in the protein structure.
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Figure 8.
Figure 8. Comparison of retinoid binding in CRABP II and
CRBP I. The Ca trace, RA and side-chain atoms of Arg111, Arg132
and Tyr134 of CRABP II have been coloured as in Figure 7, and
the solvent-accessible surface of CRABP II has been drawn in
purple. For CRBP I, the retinol has been coloured green, its
solvent-accessible surface red, and the side-chain atoms of
Gln108, Gln128 and Phe130 have been coloured green (carbon),
cyan (nitrogen) and pink (oxygen).
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The above figure is
reprinted
by permission from Cell Press:
Structure
(1994,
2,
1241-1258)
copyright 1994.
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Secondary reference #1
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Title
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Lipid-Binding proteins: a family of fatty acid and retinoid transport proteins.
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Authors
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L.Banaszak,
N.Winter,
Z.Xu,
D.A.Bernlohr,
S.Cowan,
T.A.Jones.
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Ref.
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Adv Protein Chem, 1994,
45,
89.
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PubMed id
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Secondary reference #2
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Title
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Crystallization and preliminary X-Ray analysis of recombinant bovine cellular retinoic acid-Binding protein.
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Authors
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T.Bergfors,
G.J.Kleywegt,
T.A.Jones.
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Ref.
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Acta Crystallogr D Biol Crystallogr, 1994,
50,
370-374.
[DOI no: ]
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PubMed id
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Figure 1.
Fig. 1. Retinoic acid absorbs at 350 nm. The protein-retinoic acid
spectrum can be evaluated by the ratio ,435028o. For protein
fully saturated with retinoic acid, this ratio is 2.07. When
protected from the light, the complex is stable for at least 7
months and this value remains essentially unchanged. When
exposed to light, deterioration beg'.ms within 30 min, as moni-
tored by a decrease in the absorbarice of retinoic acid at A350.
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The above figure is
reproduced from the cited reference
with permission from the IUCr
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Secondary reference #3
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Title
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Crystallographic studies on a family of cellular lipophilic transport proteins. Refinement of p2 myelin protein and the structure determination and refinement of cellular retinol-Binding protein in complex with all-Trans-Retinol.
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Authors
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S.W.Cowan,
M.E.Newcomer,
T.A.Jones.
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Ref.
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J Mol Biol, 1993,
230,
1225-1246.
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PubMed id
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Secondary reference #4
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Title
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The three-Dimensional structure of p2 myelin protein.
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Authors
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T.A.Jones,
T.Bergfors,
J.Sedzik,
T.Unge.
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Ref.
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Embo J, 1988,
7,
1597-1604.
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PubMed id
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