Retinoid isomerohydrolase

From Proteopedia

Bovine RPE65 complex with palmitate, amixustat and Fe+2 ion (PDB code 4rsc) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image Function Retinoid isomerohydrolase (RPE65) catalyzes the isomerization of trans-retinyl ester to 11-cis-retinol in the retinal pigment epithelium. This isomerization is a critical part of the visual cycle and is essential for normal vision[1]. The RPE65 inhibitor amixustat is used as a drug which modulates visual cycle activity in age-related macular degeneration[2]. RPE65 is iron-dependent. Disease Mutations in RPE65 cause Leber's congenital amaurosis and other forms of autosomal recessive retinitis pigmentosa which are associated with early-onset blindness[3]. Structural highlights The near the enzyme's membrane-embedded substrate-entry point. The [4].

3D structures of retinoid isomerohydrolase

Updated on 12-October-2023

4f2z, 4f30, 4f3a, 4f3d, 3kvc, 3fsn – bRPE65 - bovine
4ryx, 4ryy, 4ryz, 4rsc – bRPE65 + emixustat
7k88 – bRPE65 + emixustat derivative
7k89, 7l0e – bRPE65 + emixustat derivative + palmitate
4zhk, 4rse – bRPE65 + MB-200
8doc - bRPE65 + MB-003 + palmitate
5ul5, 7k8g - bRPE65 + MB-004 + palmitate
5ulg - bRPE65 + MB-008 + palmitate

References

1. ↑ Moiseyev G, Takahashi Y, Chen Y, Gentleman S, Redmond TM, Crouch RK, Ma JX. RPE65 is an iron(II)-dependent isomerohydrolase in the retinoid visual cycle. J Biol Chem. 2006 Feb 3;281(5):2835-40. Epub 2005 Nov 30. PMID:16319067 doi:http://dx.doi.org/10.1074/jbc.M508903200
2. ↑ Zhang J, Kiser PD, Badiee M, Palczewska G, Dong Z, Golczak M, Tochtrop GP, Palczewski K. Molecular pharmacodynamics of emixustat in protection against retinal degeneration. J Clin Invest. 2015 Jul 1;125(7):2781-94. doi: 10.1172/JCI80950. Epub 2015 Jun, 15. PMID:26075817 doi:http://dx.doi.org/10.1172/JCI80950
3. ↑ Cai X, Conley SM, Naash MI. RPE65: role in the visual cycle, human retinal disease, and gene therapy. Ophthalmic Genet. 2009 Jun;30(2):57-62. doi: 10.1080/13816810802626399. PMID:19373675 doi:http://dx.doi.org/10.1080/13816810802626399
4. ↑ Kiser PD, Zhang J, Badiee M, Li Q, Shi W, Sui X, Golczak M, Tochtrop GP, Palczewski K. Catalytic mechanism of a retinoid isomerase essential for vertebrate vision. Nat Chem Biol. 2015 Jun;11(6):409-15. doi: 10.1038/nchembio.1799. Epub 2015 Apr, 20. PMID:25894083 doi:http://dx.doi.org/10.1038/nchembio.1799