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Negative charge of the glutamic acid 417 residue is crucial for isomerohydrolase activity of RPE65.

ABSTRACT: RPE65 is the isomerohydrolase essential for regeneration of 11-cis retinal, the chromophore of visual pigments. Here we compared the impacts of two mutations in RPE65, E417Q identified in patients with Leber congenital amaurosis (LCA), and E417D on isomerohydrolase activity. Although both mutations decreased the stability of RPE65 and altered its sub-cellular localization, E417Q abolished isomerohydrolase activity whereas the E417D mutant retained partial enzymatic activity suggesting that the negative charge of E417 is important for RPE65 catalytic activity. Loss of charge at this position may represent a mechanism by which the E417Q mutation causes blindness in LCA patients.

SUBMITTER: Nikolaeva O

PROVIDER: S-EPMC2812700 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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Negative charge of the glutamic acid 417 residue is crucial for isomerohydrolase activity of RPE65.

Nikolaeva Olga O Takahashi Yusuke Y Moiseyev Gennadiy G Ma Jian-Xing JX

Biochemical and biophysical research communications 20091230 4

RPE65 is the isomerohydrolase essential for regeneration of 11-cis retinal, the chromophore of visual pigments. Here we compared the impacts of two mutations in RPE65, E417Q identified in patients with Leber congenital amaurosis (LCA), and E417D on isomerohydrolase activity. Although both mutations decreased the stability of RPE65 and altered its sub-cellular localization, E417Q abolished isomerohydrolase activity whereas the E417D mutant retained partial enzymatic activity suggesting that the n ...[more]

PMID: 20043869

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