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Human cellular retinaldehyde-binding protein has secondary thermal 9-cis-retinal isomerase activity.

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Publication date 2014
Author Bolze Christin S, Helbling Rachel E, Owen Robin L, Pearson Arwen R, Pompidor Guillaume, Dworkowski Florian, Fuchs Martin R, Furrer Julien, Golczak Marcin, Palczewski Krzysztof, Cascella Michele, Stocker Achim,
Project Structural and functional characterization of the retinoid visual cycle in the vertebrate eye
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Original article (peer-reviewed)

Journal Journal of the American Chemical Society
Volume (Issue) 136(1)
Page(s) 137 - 46
Title of proceedings Journal of the American Chemical Society
DOI 10.1021/ja411366w

Open Access

URL https://www.boris.unibe.ch/
Type of Open Access Repository (Green Open Access)

Abstract

Cellular 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 (1)H 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 Å 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.
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