4RSC

Crystal structure of RPE65 in complex with emixustat and palmitate

4RSC の概要

• エントリーDOI: 10.2210/pdb4rsc/pdb
• 関連するPDBエントリー: 3FSN 4F2Z 4RSE
• 分子名称: Retinoid isomerohydrolase, FE (II) ION, PALMITIC ACID, ... (5 entities in total)
• 機能のキーワード: 7-bladed beta propeller, monotopic membrane protein, non-heme iron enzyme, retinoid isomerase, smooth endoplasmic reticulum, isomerase
• 由来する生物種: Bos taurus (bovine,cow,domestic cattle,domestic cow)
• 細胞内の位置: Cytoplasm: Q28175
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 123231.68

構造登録者

Kiser, P.D.,Shi, W.,Palczewski, K. (登録日: 2014-11-07, 公開日: 2015-04-15, 最終更新日: 2023-09-20)

主引用文献

Kiser, P.D.,Zhang, J.,Badiee, M.,Li, Q.,Shi, W.,Sui, X.,Golczak, M.,Tochtrop, G.P.,Palczewski, K.
Catalytic mechanism of a retinoid isomerase essential for vertebrate vision.
Nat.Chem.Biol., 11:409-415, 2015

PubMed Abstract: Visual function in vertebrates is dependent on the membrane-bound retinoid isomerase RPE65, an essential component of the retinoid cycle pathway that regenerates 11-cis-retinal for rod and cone opsins. The mechanism by which RPE65 catalyzes stereoselective retinoid isomerization has remained elusive because of uncertainty about how retinoids bind to its active site. Here we present crystal structures of RPE65 in complex with retinoid-mimetic compounds, one of which is in clinical trials for the treatment of age-related macular degeneration. The structures reveal the active site retinoid-binding cavity located near the membrane-interacting surface of the enzyme as well as an Fe-bound palmitate ligand positioned in an adjacent pocket. With the geometry of the RPE65-substrate complex clarified, we delineate a mechanism of catalysis that reconciles the extensive biochemical and structural research on this enzyme. These data provide molecular foundations for understanding a key process in vision and pharmacological inhibition of RPE65 with small molecules.

PubMed: 25894083
DOI: 10.1038/nchembio.1799

実験手法

X-RAY DIFFRACTION (1.8 Å)