文章基本信息

标题：Expression of the Ligand-Binding Domain-Containing Region of Retinoic Acid Receptors α, β and γ in Escherichia coli and Evaluation of Ligand-Binding Selectivity
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作者：Hiroshi FUKASAWA ; Toru IIJIMA ; Hiroyuki KAGECHIKA 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：1993
卷号：16
期号：4
页码：343-348
DOI：10.1248/bpb.16.343
出版社：The Pharmaceutical Society of Japan
摘要：The complete molecule or the ligand-binding domain-containing region of each of the three subtypes of human retinoic acid receptors (hRARα, hRARβ and hRARγ) was expressed in Escherichia coli. The expressed recombinant RARs (rRARs : rRARα/E, rRARβ/E and rRARγ) showed nearly the same magnitude of binding affinity toward [³H]retinoic acid (RA) as hRARs extracted from human cells (K_a values : 6.0×10⁹ M^-1 for rRARα/E and 2.7×10¹⁰ M^-1 for both rRARβ/E and rRARγ). Therefore, the ligand-binding selectivity of the rRARs toward RA and synthetic retinoids (4-(5, 6, 7, 8-tetrahydro-5, 5, 8, 8-tetrametyl-2-naphthalenylcarbamoyl)benzoic acid (Am80), (E)-4-[3-(3, 5-di-tert-butylphenyl)-3-oxo-1-propenyl]benzoic acid (Ch55)) was examined. Am80 bound rRARα/E preferentially and showed no binding activity toward rRARγ, which is consistent with the case of hRARγ. Ch55 bound all three subtypes of rRARs, preferentially rRARβ/E. These results suggest that the intrinsic nature of the binding of each retinoid can be investigated by usage of the rRARs. However, rRARs show quantitatively different ligand-selectivity from that of hRARs : RA showed higher binding affinity toward rRARs than both Am80 and Ch55, but Ch55 binds all three subtypes of hRARs stronger than RA and Am80, which binds hRARβ stronger than RA.
关键词：retinoic acid receptor (RAR);retinoic acid;retinobenzoic acid;4-(5, 6, 7, 8-tetrahydro-5, 5, 8, 8-tetramethyl-2-naphthalenylcarbamoyl)benzoic acid (Am80);(E)-4-[3-(3, 5-di-tert-butylphenyl)-3-oxo-1-propenyl]benzoic acid (Ch55);Escherichia coli