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Direct protein–protein interactions and substrate channeling between cellular retinoic acid binding proteins and CYP 26B1
Author(s) -
Nelson Cara H.,
Peng ChiChi,
Lutz Justin D.,
Yeung Catherine K.,
Zelter Alex,
Isoherranen Nina
Publication year - 2016
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12303
Subject(s) - retinoic acid , cytochrome p450 , chemistry , biochemistry , plasma protein binding , substrate (aquarium) , binding protein , metabolism , biology , gene , ecology
Cellular retinoic acid binding proteins ( CRABP s) bind all‐trans ‐retinoic acid ( at RA ) tightly. This study aimed to determine whether at RA is channeled directly to cytochrome P450 ( CYP ) CYP 26B1 by CRABP s, and whether CRABP s interact directly with CYP 26B1. at RA bound to CRABP s (holo‐ CRABP ) was efficiently metabolized by CYP 26B1. Isotope dilution experiments showed that delivery of at RA to CYP 26B1 in solution was similar with or without CRABP . Holo‐ CRABP s had higher affinity for CYP 26B1 than free at RA , but both apo‐ CRABP s inhibited the formation of 4‐ OH ‐ RA by CYP 26B1. Similar protein–protein interactions between soluble binding proteins and CYP s may be important for other lipophilic CYP substrates.