1cbq: Difference between revisions

Revision as of 12:33, 2 May 2008

CRYSTAL STRUCTURE OF CELLULAR RETINOIC-ACID-BINDING PROTEINS I AND II IN COMPLEX WITH ALL-TRANS-RETINOIC ACID AND A SYNTHETIC RETINOID

OverviewOverview

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 StructureAbout this Structure

1CBQ is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

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 Page seeded by OCA on Fri May 2 12:33:28 2008

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OCA

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 [[Image:1cbq.jpg|left|200px]]
- {{Structure
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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'''
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 [[Category: Jones, T A.]]
 [[Category: Kleywegt, G J.]]
-[[Category: retinoic-acid transport]]
+[[Category: Retinoic-acid transport]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 12:33:28 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:18:31 2008''