title: The Biochemical Basis of Vitamin A3 Production in Arthropod Vision.
abstract: Metazoan photochemistry involves cis-trans isomerization of a retinylidene chromophore bound to G protein coupled receptors. Successful production of chromophores is critical for photoreceptor function and survival. For chromophore production, animals have to choose from more than 600 naturally occurring carotenoids and process them by oxidative cleavage and geometric isomerization of double bonds. Vertebrates employ three carotenoid cleavage oxygenases to tailor the carotenoid precursor in the synthesis of 11-cis-retinal (vitamin A1). Lepidoptera (butterfly and moth) possess only one such enzyme, NinaB, which faces the challenge to catalyze these reactions in unison to produce 11-cis-3-hydroxy-retinal (vitamin A3). We here showed that key to this multitasking is a bipartite substrate recognition site that conveys regio- and stereoselectivity for double bond processing. One side performed the specific C11, C12 cis-isomerization and preferentially binds 3-OH-β-ionone rings sites. The other side maintained a trans configuration in the resulting product and preferentially binds noncanonical ionone ring sites. Concurrent binding of carotenoids containing two cyclohexyl rings to both domains is required for specific oxidative cleavage at position C15, C15' of the substrate. The unique reaction sequence follows a dioxygenase mechanism with a carbocation/radical intermediate. This ingenious quality control system guarantees 11-cis-3-hydroxy-retinal production, the essential retinoid for insect (vitamin A3) vision.
authors.affiliation: Department of Pharmacology, Case Western Reserve University School of Medicine , Cleveland, Ohio 44106, United States.
authors.forename: Darwin
authors.initials: D
authors.lastname: Babino
authors.affiliation: Department of Pharmacology, Case Western Reserve University School of Medicine , Cleveland, Ohio 44106, United States.
authors.forename: Marcin
authors.initials: M
authors.lastname: Golczak
authors.affiliation: Department of Pharmacology, Case Western Reserve University School of Medicine , Cleveland, Ohio 44106, United States.
authors.forename: Philip D
authors.initials: PD
authors.lastname: Kiser
authors.affiliation: Department of Human Nutrition and Health, DSM Nutritional Products , Kaiseraugst 4303, Switzerland.
authors.forename: Adrian
authors.initials: A
authors.lastname: Wyss
authors.affiliation: Department of Pharmacology, Case Western Reserve University School of Medicine , Cleveland, Ohio 44106, United States.|Cleveland Center for Membrane and Structural Biology, Case Western Reserve University School of Medicine , Cleveland, Ohio 44106, United States.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Palczewski
authors.affiliation: Department of Pharmacology, Case Western Reserve University School of Medicine , Cleveland, Ohio 44106, United States.
authors.forename: Johannes
authors.initials: J
authors.lastname: von Lintig
mesh_terms: D000818:Animals; D001181:Arthropods / Q000378:metabolism*; D002384:Catalysis; D010084:Oxidation-Reduction; D014801:Vitamin A / Q000096:biosynthesis*
chemical_list: D014801:Vitamin A
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