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

DOI: 10.1021/ja411366w
PMID: 24328211

Authors: Christin S. Bolze (University of Bern) , Rachel E. Helbling (University of Bern) , Robin Owen (Diamond Light Source) , Arwen Pearson (University of Leeds) , Guillaume Pompidor (Swiss Light Source) , Florian Dworkowski (Swiss Light Source) , Martin R. Fuchs (Swiss Light Source) , Julien Furrer (University of Bern) , Marcin Golczak (Case Western Reserve University) , Krzysztof Palczewski (Case Western Reserve University) , Michele Cascella (University of Bern) , Achim Stocker (University of Bern)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of The American Chemical Society , VOL 136 (1) , PAGES 137 - 146

State: Published (Approved)
Published: January 2014

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 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 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.

Subject Areas: Biology and Bio-materials, Chemistry

Facility: X06DA PXIII (PSI Villigen) at Swiss Light Source

Added On: 10/06/2014 11:41

Documents:
ja411366w.pdf

Discipline Tags:

Health & Wellbeing Biochemistry Chemistry Ophthalmology Life Sciences & Biotech

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