title: Direct protein-protein interactions and substrate channeling between cellular retinoic acid binding proteins and CYP26B1.
abstract: Cellular retinoic acid binding proteins (CRABPs) bind all-trans-retinoic acid (atRA) tightly. This study aimed to determine whether atRA is channeled directly to cytochrome P450 (CYP) CYP26B1 by CRABPs, and whether CRABPs interact directly with CYP26B1. atRA bound to CRABPs (holo-CRABP) was efficiently metabolized by CYP26B1. Isotope dilution experiments showed that delivery of atRA to CYP26B1 in solution was similar with or without CRABP. Holo-CRABPs had higher affinity for CYP26B1 than free atRA, but both apo-CRABPs inhibited the formation of 4-OH-RA by CYP26B1. Similar protein-protein interactions between soluble binding proteins and CYPs may be important for other lipophilic CYP substrates.
authors.affiliation: Department of Pharmaceutics, University of Washington, Seattle, WA, USA.
authors.forename: Cara H
authors.initials: CH
authors.lastname: Nelson
authors.affiliation: Department of Pharmaceutics, University of Washington, Seattle, WA, USA.
authors.forename: Chi-Chi
authors.initials: CC
authors.lastname: Peng
authors.affiliation: Department of Pharmaceutics, University of Washington, Seattle, WA, USA.
authors.forename: Justin D
authors.initials: JD
authors.lastname: Lutz
authors.affiliation: Department of Pharmaceutics, University of Washington, Seattle, WA, USA.
authors.forename: Catherine K
authors.initials: CK
authors.lastname: Yeung
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, WA, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Zelter
authors.affiliation: Department of Pharmaceutics, University of Washington, Seattle, WA, USA.
authors.forename: Nina
authors.initials: N
authors.lastname: Isoherranen
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007700:Kinetics; D060066:Protein Interaction Maps / Q000235:genetics*; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism*; D000072516:Retinoic Acid 4-Hydroxylase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D054840:Retinol-Binding Proteins, Cellular / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D014212:Tretinoin / Q000737:chemistry / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D018168:Receptors, Retinoic Acid; D054840:Retinol-Binding Proteins, Cellular; C082927:retinoic acid binding protein I, cellular; C082928:retinoic acid binding protein II, cellular; D014212:Tretinoin; C000607079:CYP26B1 protein, human; D000072516:Retinoic Acid 4-Hydroxylase
keywords: binding proteins; cytochrome P450; retinoic acid; substrate channeling