title: Structural basis of carotenoid cleavage: from bacteria to mammals.
abstract: Carotenoids and their metabolic derivatives serve critical functions in both prokaryotic and eukaryotic cells, including pigmentation, photoprotection and photosynthesis as well as cell signaling. These organic compounds are also important for visual function in vertebrate and non-vertebrate organisms. Enzymatic transformations of carotenoids to various apocarotenoid products are catalyzed by a family of evolutionarily conserved, non-heme iron-containing enzymes named carotenoid cleavage oxygenases (CCOs). Studies have revealed that CCOs are critically involved in carotenoid homeostasis and essential for the health of organisms including humans. These enzymes typically display a high degree of regio- and stereo-selectivity, acting on specific positions of the polyene backbone located in their substrates. By oxidatively cleaving and/or isomerizing specific double bonds, CCOs generate a variety of apocarotenoid isomer products. Recent structural studies have helped illuminate the mechanisms by which CCOs mobilize their lipophilic substrates from biological membranes to perform their characteristic double bond cleavage and/or isomerization reactions. In this review, we aim to integrate structural and biochemical information about CCOs to provide insights into their catalytic mechanisms.
authors.affiliation: Department of Pharmacology, School of Medicine, Case Western Reserve University, 2109 Adelbert Rd, Cleveland, OH 44106-4965, USA.
authors.forename: Xuewu
authors.initials: X
authors.lastname: Sui
authors.forename: Philip D
authors.initials: PD
authors.lastname: Kiser
authors.forename: Johannes von
authors.initials: Jv
authors.lastname: Lintig
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Palczewski
mesh_terms: D000818:Animals; D001419:Bacteria / Q000737:chemistry* / Q000378:metabolism; D018407:Bacterial Physiological Phenomena; D002338:Carotenoids / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D002384:Catalysis; D006801:Humans; D008322:Mammals / Q000378:metabolism / Q000502:physiology; D010105:Oxygenases / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D002338:Carotenoids; D010105:Oxygenases; C500451:carotenoid oxygenase; C004984:apocarotenal
keywords: ACO; Apocarotenoid; Carotenoid; Carotenoid oxygenase; RPE65; VP14