Identification of conserved histidines and glutamic acid as key residues for isomerohydrolase activity of RPE65, an enzyme of the visual cycle in the retinal pigment epithelium
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We have recently reported that RPE65 from the retinal pigment epithelium is the isomerohydrolase, a critical enzyme in the visual cycle for regeneration of 11‐cis retinal, the chromophore for visual pigments. Here, we demonstrated that mutation of any one of the absolutely conserved four histidine and one glutamic acid residues to alanine in RPE65 abolished its isomerohydrolase activity. Substitution of the conserved glutamic acid with glutamine also resulted in loss of the activity. Moreover, these mutations significantly reduced protein stability of RPE65. These results indicate that these conserved residues are essential for the isomerohydrolase activity of RPE65 and its stability.
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Mutations in RPE65 iron-coordinating His residues, second-sphere Glu residues, and third-sphere residues that hydrogen bond to second-sphere Glu residues abolish or greatly reduce RPE65 activity.
“Mutations in the iron-coordinating His residues,447 the second sphere Glu residues,472−474 and even a third sphere of residues that form hydrogen bonding interactions with the second-sphere Glu residues468,475 either abolish or greatly reduce RPE65 activity.”
From Chemistry of the Retinoid (Visual) Cycle (2014) · cites this paper as [474]
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BackgroundMethodSelf-citationIdentification of the Key Residues Determining the Product Specificity of Isomerohydrolase
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Self-citation
- Authors
- Takahashi, Y., Moiseyev, G., Chen, Y., & Ma, J.-X.
- Affiliations
- University of Oklahoma Health Sciences Center (US)
- Corresponding author
- Ma, Jian-xing
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 2005-09-16
- Volume
- 579
- Issue
- 24
- Pages
- 5414-5418
- ISSN
- 0014-5793 (ISSN-L)
- 1873-3468
- OpenAlex
- W2081310089
- Cited by
- 54
- References
- 27
- Citations by year
- 2025: 1 · 2023: 1 · 2022: 1 · 2021: 3 · 2020: 3 · 2019: 3 · 2017: 1 · 2016: 5 · 2015: 2 · 2014: 5 · 2013: 4 · 2012: 3
- FWCI
- 1.38
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- FEBS Letters (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Oklahoma Center for the Advancement of Science and Technology (EY012231)
- National Institutes of Health (EY015650)
- University of Oklahoma Health Sciences Center (EY012231)
- National Eye Institute (EY-012231, EY 015650, R01EY012231)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Photoreceptor and optogenetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Keywords
- RPE65, visual cycle, 11-cis-retinal regeneration, conserved histidine residues, site-directed mutagenesis, protein stability, retinal pigment epithelium, glutamine substitution
- MeSH terms
- Retinoid Isomerohydrolase, Carrier Proteins, Catalysis, Eye Proteins, Histidine, Humans, Hydrolases, Models, Molecular, Pigment Epithelium of Eye, Mutagenesis, Site-Directed, Glutamic Acid, cis-trans-Isomerases
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