A5088294618- Retinal Development and Disorders
- Retinoids in leukemia and cellular processes
- Retinal Diseases and Treatments
- Photoreceptor and optogenetics research
- Photosynthetic Processes and Mechanisms
- Receptor Mechanisms and Signaling
- Metal-Catalyzed Oxygenation Mechanisms
- Antioxidant Activity and Oxidative Stress
- Cellular transport and secretion
- Enzyme Structure and Function
- Photochromic and Fluorescence Chemistry
- Advanced Fluorescence Microscopy Techniques
- Computational Drug Discovery Methods
- Crystallization and Solubility Studies
- Natural product bioactivities and synthesis
- Lipid Membrane Structure and Behavior
- Biochemical effects in animals
- Protein Structure and Dynamics
- Neuroscience and Neuropharmacology Research
- Solid-state spectroscopy and crystallography
- Microbial metabolism and enzyme function
- Neuropeptides and Animal Physiology
- Cancer, Hypoxia, and Metabolism
- Monoclonal and Polyclonal Antibodies Research
- Crystal structures of chemical compounds
University of California, Irvine
2019-2025
VA Long Beach Healthcare System
2019-2024
California State University, Long Beach
2024
Long Beach Medical Center
2024
Tibor Rubin VA Medical Center
2024
Louis Stokes Cleveland VA Medical Center
2015-2023
The California Eye Institute
2021
Case Western Reserve University
2010-2019
University School
2016-2019
Weatherford College
2019
Vertebrate vision is maintained by the retinoid (visual) cycle, a complex enzymatic pathway that operates in retina to regenerate visual chromophore, 11- cis -retinal. A key enzyme this microsomal membrane protein RPE65. This catalyzes conversion of all- trans -retinyl esters -retinol retinal pigment epithelium (RPE). Mutations RPE65 are known be responsible for subset cases most common form childhood blindness, Leber congenital amaurosis (LCA). Although isomerase activity has been...
Abstract G protein-coupled receptors (GPCRs) activate heterotrimeric proteins by mediating a GDP to GTP exchange in the Gα subunit. This leads dissociation of heterotrimer into Gα-GTP and Gβγ dimer. The dimer each regulate variety downstream pathways control various aspects human physiology. Dysregulated Gβγ-signaling is central element neurological cancer-related anomalies. However, also serves as negative regulator that essential for protein inactivation, thus has potential numerous side...
Vitamin A serves essential functions in mammalian biology as a signaling molecule and chromophore. This lipid can be synthesized from more than 50 putative dietary provitamin precursor molecules which contain at least one unsubstituted β-ionone ring. We here scrutinized the enzymatic properties substrate specificities of two structurally related carotenoid cleavage dioxygenases (CCDs) catalyze this synthesis. Recombinant BCO1 split substrates across C15,C15′ double bond adjacent to canonical...
In daylight, demand for visual chromophore (11-cis-retinal) exceeds supply by the classical cycle. This shortfall is compensated, in part, retinal G-protein-coupled receptor (RGR) photoisomerase, which expressed both pigment epithelium (RPE) and Müller cells. The relative contributions of these two cellular pools RGR to maintenance photoreceptor light responses are not known. Here, we use a cell-specific gene reactivation approach elucidate kinetics RGR-mediated recovery following exposure....
In vertebrate retinal photoreceptors, the absorption of light by rhodopsin leads to photoisomerization 11-cis-retinal its all-trans isomer. To sustain vision, a metabolic system evolved that recycles all-trans-retinal back 11-cis-retinal. The importance this visual (retinoid) cycle is underscored fact mutations in genes encoding components induce wide spectrum diseases characterized abnormal levels specific retinoid intermediates. addition, intense illumination can produce by-products are...
Emixustat is a visual cycle modulator that has entered clinical trials as treatment for age-related macular degeneration (AMD). This molecule been proposed to inhibit the isomerase RPE65, thereby slowing regeneration of 11-cis-retinal and reducing production retinaldehyde condensation byproducts may be involved in AMD pathology. Previously, we reported all-trans-retinal (atRAL) directly cytotoxic certain primary amine compounds transiently sequester atRAL via Schiff base formation ameliorate...
RPE65 is a key metalloenzyme responsible for maintaining visual function in vertebrates. Despite extensive research on this membrane-bound retinoid isomerase, fundamental questions regarding its enzymology remain unanswered. Here, we report the crystal structure of membrane-like environment. These crystals, obtained from enzymatically active, nondelipidated protein, displayed an unusual packing arrangement wherein embedded lipid–detergent sheet. Structural differences between delipidated and...
Important in regulating the uptake, storage, and metabolism of retinoids, cellular retinol-binding protein 1 (CRBP1) is essential for trafficking vitamin A through cytoplasm. However, molecular details ligand uptake targeted release by CRBP1 remain unclear. Here we report first structure a ligand-free form as well ultra-high resolution structures this bound to either all-trans-retinol or retinylamine, latter therapeutic retinoid that prevents light-induced retinal degeneration....
Photoisomerization of the 11-cis-retinal chromophore rod and cone visual pigments to an all-trans-configuration is initiating event for vision in vertebrates. The regeneration 11-cis-retinal, necessary sustained function, endergonic process normally conducted by specialized enzyme systems. However, also can be formed through reverse photoisomerization from all-trans-retinal. A nonvisual opsin known as retinal pigment epithelium (RPE)-retinal G-protein–coupled receptor (RGR) was previously...
Photoreceptors rely on distinct membrane compartments to support their specialized function. Unlike protein localization, identification of critical differences in content has not yet been expanded lipids, due the difficulty isolating domain-specific samples. We have overcome this by using SMA coimmunopurify proteins and native lipids from two regions photoreceptor ROS disks. Each sample's copurified were subjected untargeted lipidomic fatty acid analysis. Extensive between center...
Abstract Rhodopsin is a prototypical G protein-coupled receptor (GPCR) critical for vertebrate vision. Research on GPCR signaling states has been facilitated using llama-derived nanobodies (Nbs), some of which bind to the intracellular surface allosterically modulate receptor. Extracellularly binding allosteric have also investigated, but structural basis their activity not resolved date. Here, we report library Nbs that extracellular rhodopsin and thermodynamics its activation process....