4ciz
From Proteopedia
Crystal structure of the complex of the Cellular Retinal Binding Protein with 9-cis-retinal
Structural highlights
Disease[RLBP1_HUMAN] Defects in RLBP1 are a cause of retinitis pigmentosa autosomal recessive (ARRP) [MIM:268000]. RP leads to degeneration of retinal photoreceptor cells. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well.[1] Defects in RLBP1 are the cause of Bothnia retinal dystrophy (BRD) [MIM:607475]; also known as Vasterbotten dystrophy. Affected individuals show night blindness from early childhood with features consistent with retinitis punctata albescens and macular degeneration.[2] Defects in RLBP1 are the cause of rod-cone dystrophy Newfoundland (NFRCD) [MIM:607476]. NFRCD is a retinal dystrophy reminiscent of retinitis punctata albescens but with a substantially lower age at onset and more-rapid and distinctive progression. Rod-cone dystrophies results from initial loss of rod photoreceptors, later followed by cone photoreceptors loss.[3] Defects in RLBP1 are a cause of retinitis punctata albescens (RPA) [MIM:136880]. A rare form of stationary night blindness characterized by a delay in the regeneration of cone and rod photopigments. Function[RLBP1_HUMAN] Soluble retinoid carrier essential the proper function of both rod and cone photoreceptors. Participates in the regeneration of active 11-cis-retinol and 11-cis-retinaldehyde, from the inactive 11-trans products of the rhodopsin photocycle and in the de novo synthesis of these retinoids from 11-trans metabolic precursors. The cycling of retinoids between photoreceptor and adjacent pigment epithelium cells is known as the 'visual cycle'.[4] Publication Abstract from PubMedCellular retinaldehyde-binding protein (CRALBP) chaperones 11-cis-retinal to convert opsin receptor molecules into photosensitive retinoid pigments of the eye. We report a thermal secondary isomerase activity of CRALBP when bound to 9-cis-retinal. UV/vis and 1H NMR spectroscopy were used to characterize the product as 9,13-dicis-retinal. The X-ray structure of the CRALBP mutant R234W:9-cis-retinal complex at 1.9 A resolution revealed a niche in the binding pocket for 9-cis-aldehyde different from that reported for 11-cis-retinal. Combined computational, kinetic, and structural data lead us to propose an isomerization mechanism catalyzed by a network of buried waters. Our findings highlight a specific role of water molecules in both CRALBP-assisted specificity toward 9-cis-retinal and its thermal isomerase activity yielding 9,13-dicis-retinal. Kinetic data from two point mutants of CRALBP support an essential role of Glu202 as the initial proton donor in this isomerization reaction. Human Cellular Retinaldehyde-Binding Protein Has Secondary Thermal 9-cis-Retinal Isomerase Activity.,Bolze CS, Helbling RE, Owen RL, Pearson AR, Pompidor G, Dworkowski F, Fuchs MR, Furrer J, Golczak M, Palczewski K, Cascella M, Stocker A J Am Chem Soc. 2013 Dec 20. PMID:24328211[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Homo sapiens | Large Structures | Bolze CS | Cascella M | Dworkowski F | Fuchs MR | Furrer J | Golczak M | Helbling RE | Owen RL | Palczewski K | Pearson AR | Pompidor G | Stocker A
