ArticleBiochemistry2012
Identification of the key residues determining the product specificity of isomerohydrolase.
Article in Biochemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 0 citations in OpenAlex.
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- The cone visual cycle and its disorders: insights from zebrafish.Frontiers in molecular neuroscience · 2025Review
- Double-duty isomerases: a case study of isomerization-coupled enzymatic catalysis.Trends in biochemical sciences · 2024Review
- Ablation of Fatty Acid Transport Protein-4 Enhances Cone Survival, M-cone Vision, and Synthesis of Cone-Tropic 9-The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Carotenoid cleavage enzymes evolved convergently to generate the visual chromophore.Nature chemical biology · 2024Article
- The Role of Vitamin A in Retinal Diseases.International journal of molecular sciences · 2022Review
- Structural biology of 11-The Biochemical journal · 2018Review
- Reduced Carotenoid and Retinoid Concentrations and Altered Lycopene Isomer Ratio in Plasma of Atopic Dermatitis Patients.Nutrients · 2018Article
- A Dominant Mutation in Rpe65, D477G, Delays Dark Adaptation and Disturbs the Visual Cycle in the Mutant Knock-In Mice.The American journal of pathology · 2017Article
- Key Residues for Catalytic Function and Metal Coordination in a Carotenoid Cleavage Dioxygenase.The Journal of biological chemistry · 2016Article
- Catalytic mechanism of a retinoid isomerase essential for vertebrate vision.Nature chemical biology · 2015Article
- Analysis of carotenoid isomerase activity in a prototypical carotenoid cleavage enzyme, apocarotenoid oxygenase (ACO).The Journal of biological chemistry · 2014Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The efficient recycling of the chromophore of visual pigments, 11-cis-retinal, through the retinoid visual cycle is an essential process for maintaining normal vision. RPE65 is the isomerohydrolase in retinal pigment epithelium and generates predominantly 11-cis-retinol (11cROL) and a minor amount of 13-cis-retinol (13cROL), from all-trans-retinyl ester (atRE). We recently identified and characterized novel homologues of RPE65, RPE65c, and 13-cis-isomerohydrolase (13cIMH), which are expressed in the zebrafish inner retina and brain, respectively. Although these two homologues have 97% identical amino acid sequences, they exhibit distinct product specificities. Under the same assay conditions, RPE65c generated predominantly 11cROL, similar to RPE65, while 13cIMH generated exclusively 13cROL from atRE substrate. To study the impacts of the key residues determining the isomerization product specificity of RPE65, we replaced candidate residues by site-directed mutagenesis in RPE65c and 13cIMH. Point mutations at residues Tyr58, Phe103, and Leu133 in RPE65c resulted in significantly altered isomerization product specificities. In particular, our results showed that residue 58 is a primary determinant of isomerization specificity, because the Y58N mutation in RPE65c and its reciprocal N58Y mutation in 13cIMH completely reversed the respective enzyme isomerization product specificities. These findings will contribute to the elucidation of molecular mechanisms underlying the isomerization reaction catalyzed by RPE65.
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