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Retinal Pigment Epithelium 65 (Retinoid Isomerohydrolase) complex with (R/S)-emixustat and palmitate

Retinal pigment epithelium 65 (RPE65) also known as retinoid isomerohydrolase is a 65 kDa enzyme located within the human retinal pigment epithelium cells responsible for the chemical conversion of all-trans-retinyl ester to 11-cis-retinol in the visual cycle.

(PLACEHOLDER This is a default text for your page Ivan E. Wang/Sandbox 1. Click above on edit this page to modify. Be careful with the < and > signs.

You may include any references to papers as in: the use of JSmol in Proteopedia ^[1] or to the article describing Jmol ^[2] to the rescue.)

1 Function
- 1.1 Structural Features of RPE65
- 1.2 Enzymatic Catalyzed Reaction
2 Protein-Ligand Interaction
3 Disease Implications
4 Medical Relevance

Function

Structural Features of RPE65

Enzymatic Catalyzed Reaction

Protein-Ligand Interaction

Endogenous Ligand

Exogenous Ligand

(R)-Emixustat (ACU-4429)

(R)-emixustat (ACU-4429) is an investigational small molecule inhibitor of RPE65 first invented by a British-American chemist, Ian L. Scott. Formulated as an hydrochloride salt, (R)-emixustat hydrochloride is taken by mouth and functions as a visual cycle modulator (VCM) to reduce toxic retinal byproducts such as A2E.

In 2008, Acucela Inc. partnered with Otsuka Pharmaceutical Company for the continued development of (R)-emixustat as a potential inhibitor of RPE65. Currently (R)-emixustat is in Phase III clinical trials in the United States for the potential treatment of Stargard's disease, a juvenile form of atrophic (dry) age dependent macular degeneration (AMD). Additionally, (R)-emixustat is investigated as potential therapy for diabetic retinopathy and diabetic macular edema.

(S)-Emixustat

R/S Enantiomers Differences

Disease Implications

Medical Relevance

This is a sample scene created with SAT to by Group, and another to make of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

References

↑ Hanson, R. M., Prilusky, J., Renjian, Z., Nakane, T. and Sussman, J. L. (2013), JSmol and the Next-Generation Web-Based Representation of 3D Molecular Structure as Applied to Proteopedia. Isr. J. Chem., 53:207-216. doi:http://dx.doi.org/10.1002/ijch.201300024
↑ Herraez A. Biomolecules in the computer: Jmol to the rescue. Biochem Mol Biol Educ. 2006 Jul;34(4):255-61. doi: 10.1002/bmb.2006.494034042644. PMID:21638687 doi:10.1002/bmb.2006.494034042644

Proteopedia Page Contributors and Editors (what is this?)

Ivan E. Wang

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 '''Retinal Pigment Epithelium 65 (Retinoid Isomerohydrolase) complex with (''R''/''S'')-emixustat and palmitate'''
-<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
+<StructureSection load='4rsc' size='340' side='right' caption='Emixustat bound in the active site of RPE65' scene=''>
 Retinal pigment epithelium 65 (RPE65) also known as retinoid isomerohydrolase is a 65 kDa enzyme located within the human retinal pigment epithelium cells responsible for the chemical conversion of ''all-trans''-retinyl ester to ''11-cis''-retinol in the visual cycle.