4CJ6

Crystal structure of the complex of the Cellular Retinal Binding Protein Mutant R234W with 9-cis-retinal

4CJ6 の概要

• エントリーDOI: 10.2210/pdb4cj6/pdb
• 関連するPDBエントリー: 4CIZ
• 分子名称: RETINALDEHYDE-BINDING PROTEIN 1, RETINAL (3 entities in total)
• 機能のキーワード: isomerase, visual cycle, 9-cis-retinal
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Cytoplasm: P12271
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 36827.60

構造登録者

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. (登録日: 2013-12-19, 公開日: 2014-01-08, 最終更新日: 2023-12-20)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.896 Å)