4CIZ

Crystal structure of the complex of the Cellular Retinal Binding Protein with 9-cis-retinal

Summary for 4CIZ

• Entry DOI: 10.2210/pdb4ciz/pdb
• Descriptor: RETINALDEHYDE-BINDING PROTEIN 1, RETINAL, L(+)-TARTARIC ACID, ... (4 entities in total)
• Functional Keywords: retinaldehyde binding protein, visual cycle, 9-cis-retinal, cellular retinal binding protein, isomerase
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm: P12271
• Total number of polymer chains: 1
• Total formula weight: 36948.68

Authors

Bolze, C.S.,Helbling, R.E.,Owen, R.L.,Pearson, A.R.,Pompidor, G.,Dworkowski, F.,Fuchs, M.R.,Furrer, J.,Golczak, M.,Palczewski, K.,Cascella, M.,Stocker, A. (deposition date: 2013-12-18, release date: 2014-01-08, Last modification date: 2023-12-20)

Primary citation

Bolze, C.S.,Helbling, R.E.,Owen, R.L.,Pearson, A.R.,Pompidor, G.,Dworkowski, F.,Fuchs, M.R.,Furrer, J.,Golczak, M.,Palczewski, K.,Cascella, M.,Stocker, A.
Human Cellular Retinaldehyde-Binding Protein Has Secondary Thermal 9-Cis-Retinal Isomerase Activity.
J.Am.Chem.Soc., 136:137-, 2014

PubMed 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.

PubMed: 24328211
DOI: 10.1021/JA411366W

Experimental method

X-RAY DIFFRACTION (3.403 Å)