1cbr
From Proteopedia
(New page: 200px<br /><applet load="1cbr" size="450" color="white" frame="true" align="right" spinBox="true" caption="1cbr, resolution 2.9Å" /> '''CRYSTAL STRUCTURE OF ...) |
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| - | [[Image:1cbr.jpg|left|200px]]<br /><applet load="1cbr" size=" | + | [[Image:1cbr.jpg|left|200px]]<br /><applet load="1cbr" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1cbr, resolution 2.9Å" /> | caption="1cbr, resolution 2.9Å" /> | ||
'''CRYSTAL STRUCTURE OF CELLULAR RETINOIC-ACID-BINDING PROTEINS I AND II IN COMPLEX WITH ALL-TRANS-RETINOIC ACID AND A SYNTHETIC RETINOID'''<br /> | '''CRYSTAL STRUCTURE OF CELLULAR RETINOIC-ACID-BINDING PROTEINS I AND II IN COMPLEX WITH ALL-TRANS-RETINOIC ACID AND A SYNTHETIC RETINOID'''<br /> | ||
==Overview== | ==Overview== | ||
| - | BACKGROUND: Retinoic acid (RA) plays a fundamental role in diverse | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1CBR is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with REA as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1CBR is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=REA:'>REA</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CBR OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Bergfors, T.]] | [[Category: Bergfors, T.]] | ||
| - | [[Category: Jones, T | + | [[Category: Jones, T A.]] |
| - | [[Category: Kleywegt, G | + | [[Category: Kleywegt, G J.]] |
[[Category: REA]] | [[Category: REA]] | ||
[[Category: retinoic-acid transport]] | [[Category: retinoic-acid transport]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:04:26 2008'' |
Revision as of 10:04, 21 February 2008
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CRYSTAL STRUCTURE OF CELLULAR RETINOIC-ACID-BINDING PROTEINS I AND II IN COMPLEX WITH ALL-TRANS-RETINOIC ACID AND A SYNTHETIC RETINOID
Overview
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.
About this Structure
1CBR is a Single protein structure of sequence from Mus musculus with as ligand. Full crystallographic information is available from OCA.
Reference
Crystal structures of cellular retinoic acid binding proteins I and II in complex with all-trans-retinoic acid and a synthetic retinoid., Kleywegt GJ, Bergfors T, Senn H, Le Motte P, Gsell B, Shudo K, Jones TA, Structure. 1994 Dec 15;2(12):1241-58. PMID:7704533
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