3fsn
From Proteopedia
Crystal structure of RPE65 at 2.14 angstrom resolution
Structural highlights
Function[RPE65_BOVIN] Plays important roles in the production of 11-cis retinal and in visual pigment regeneration. The soluble form binds vitamin A (all-trans-retinol), making it available for LRAT processing to all-trans-retinyl ester. The membrane form, palmitoylated by LRAT, binds all-trans-retinyl esters, making them available for IMH (isomerohydrolase) processing to all-cis-retinol. The soluble form is regenerated by transferring its palmitoyl groups onto 11-cis-retinol, a reaction catalyzed by LRAT. The enzymatic activity is linearly dependent of the expression levels and membrane association.[1] [2] [3] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedVertebrate vision is maintained by the retinoid (visual) cycle, a complex enzymatic pathway that operates in the retina to regenerate the visual chromophore, 11-cis-retinal. A key enzyme in this pathway is the microsomal membrane protein RPE65. This enzyme catalyzes the conversion of all-trans-retinyl esters to 11-cis-retinol in the retinal pigment epithelium (RPE). Mutations in RPE65 are known to be responsible for a subset of cases of the most common form of childhood blindness, Leber congenital amaurosis (LCA). Although retinoid isomerase activity has been attributed to RPE65, its catalytic mechanism remains a matter of debate. Also, the manner in which RPE65 binds to membranes and extracts retinoid substrates is unclear. To gain insight into these questions, we determined the crystal structure of native bovine RPE65 at 2.14-A resolution. The structural, biophysical, and biochemical data presented here provide the framework needed for an in-depth understanding of the mechanism of catalytic isomerization and membrane association, in addition to the role mutations that cause LCA have in disrupting protein function. Crystal structure of native RPE65, the retinoid isomerase of the visual cycle.,Kiser PD, Golczak M, Lodowski DT, Chance MR, Palczewski K Proc Natl Acad Sci U S A. 2009 Oct 13;106(41):17325-30. Epub 2009 Oct 5. PMID:19805034[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Bos taurus | Large Structures | RCSB PDB Molecule of the Month | Retinoid isomerohydrolase | Rhodopsin | Kiser, P D | Lodowski, D T | Palczewski, K | 7-bladed beta-propeller | Cell membrane | Isomerase | Isomerohydrolase | Lipoprotein | Membrane | Palmitate | Palmitoylation | Sensory transduction | Vision
