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Contents

Introduction to the RPE65

Figure 1: Emixustat and palmitate bound in the active site of RPE65

Structure and Activity

Classification and Structural Analysis of RPE65

Classification nomenclature for RPE65 is as follow according to <insert classification type>

Retinal pigment epithelium 65 (RPE65) resembles a 7-bladed propeller with two deep binding pockets that contains a lipophilic binding pocket (which binds to endogenous palmitoyl acid) as well as an charged iron(II) atom stabilized by 4 histidine residues (His180, His241, His313 and His527) which binds to the carboxylic acid functional group of endogenous palmitoyl acid.


Enzymatic Activity of RPE65

(PLACEHOLDER)

Figure 2: The canonical Visual Cycle in Humans
Figure 2: The canonical Visual Cycle in Humans [1]


Protein-Ligand Interaction

Endogenous Ligand

(PLACEHOLDER)

Exogenous Ligand

(R)-Emixustat (ACU-4429)

Figure 3:(R)-emixustat and palmitate bound in the active site of RPE65

(S)-Emixustat

Figure 4:(S)-emixustat and palmitate bound in the active site of RPE65

R/S Enantiomers Differences

(PLACEHOLDER)

Disease Implications

(PLACEHOLDER)

Medical Relevance

Dry (atrophic) age related macular degeneration

Stargadt's Disease

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

  1. Shin Y, Moiseyev G, Petrukhin K, Cioffi CL, Muthuraman P, Takahashi Y, Ma JX. A novel RPE65 inhibitor CU239 suppresses visual cycle and prevents retinal degeneration. Biochim Biophys Acta Mol Basis Dis. 2018 Jul;1864(7):2420-2429. doi:, 10.1016/j.bbadis.2018.04.014. Epub 2018 Apr 21. PMID:29684583 doi:http://dx.doi.org/10.1016/j.bbadis.2018.04.014

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Ivan E. Wang

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