4F2Z

Crystal structure of RPE65 in a lipid environment

Summary for 4F2Z

• Entry DOI: 10.2210/pdb4f2z/pdb
• Related: 3FSN 4F30 4F3A 4F3D
• Descriptor: Retinoid isomerohydrolase, FE (II) ION (2 entities in total)
• Functional Keywords: monotopic membrane protein, metalloprotein, non-heme iron protein, beta-propeller, smooth er membrane, isomerase, hydrolase
• Biological source: Bos taurus (bovine)
• Cellular location: Cytoplasm: Q28175
• Total number of polymer chains: 2
• Total formula weight: 122192.08

Authors

Kiser, P.D.,Shi, W.,Palczewski, K. (deposition date: 2012-05-08, release date: 2012-10-03, Last modification date: 2023-09-13)

Primary citation

Kiser, P.D.,Farquhar, E.R.,Shi, W.,Sui, X.,Chance, M.R.,Palczewski, K.
Structure of RPE65 isomerase in a lipidic matrix reveals roles for phospholipids and iron in catalysis.
Proc.Natl.Acad.Sci.USA, 109:E2747-E2756, 2012

PubMed Abstract: RPE65 is a key metalloenzyme responsible for maintaining visual function in vertebrates. Despite extensive research on this membrane-bound retinoid isomerase, fundamental questions regarding its enzymology remain unanswered. Here, we report the crystal structure of RPE65 in a membrane-like environment. These crystals, obtained from enzymatically active, nondelipidated protein, displayed an unusual packing arrangement wherein RPE65 is embedded in a lipid-detergent sheet. Structural differences between delipidated and nondelipidated RPE65 uncovered key residues involved in substrate uptake and processing. Complementary iron K-edge X-ray absorption spectroscopy data established that RPE65 as isolated contained a divalent iron center and demonstrated the presence of a tightly bound ligand consistent with a coordinated carboxylate group. These results support the hypothesis that the Lewis acidity of iron could be used to promote ester dissociation and generation of a carbocation intermediate required for retinoid isomerization.

PubMed: 23012475
DOI: 10.1073/pnas.1212025109

Experimental method

X-RAY DIFFRACTION (3 Å)