| ○種別 (必須): | □ | 学術論文 (審査論文)
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| ○言語 (必須): | □ | 英語
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| ○組織 (推奨): |
| ○著者 (必須): | 1. | (英) Kragh-Hansen U (日) (読)
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| 2. | (英) Minchiotti L (日) (読)
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| 3. | (英) Coletta A (日) (読)
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| 4. | (英) Bienk K (日) (読)
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| 5. | (英) Galliano M (日) (読)
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| 6. | (英) Schiøtt B (日) (読)
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| 7. | (英) Iwao Y (日) (読)
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| 8. | 異島 優
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| 9. | (英) Otagiri M (日) (読)
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| ○題名 (必須): | □ | (英) Mutants and molecular dockings reveal that the primary L-thyroxine binding site in human serum albumin is not the one which can cause familial dysalbuminemic hyperthyroxinemia (日)
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| ○要約 (任意): | □ | (英) Natural mutations of R218 in human serum albumin (HSA) result in an increased affinity for L-thyroxine and lead to the autosomal dominant condition of familial dysalbuminemic hyperthyroxinemia. Binding was studied by equilibrium dialysis and computer modeling. Ten of 32 other isoforms tested had modified high-affinity hormone binding. L-thyroxine has been reported to bind to four sites (Tr) in HSA; Tr1 and Tr4 are placed in the N-terminal and C-terminal part of the protein, respectively. Site-directed mutagenesis gave new information about all the sites. It is widely assumed that Tr1 is the primary hormone site, and that this site, on a modified form, is responsible for the above syndrome, but the binding experiments with the genetic variants and displacement studies with marker ligands indicated that the primary site is Tr4. This new assignment of the high-affinity site was strongly supported by results of MM-PBSA analyses and by molecular docking performed on relaxed protein structure. However, dockings also revealed that mutating R218 for a smaller amino acid increases the affinity of Tr1 to such an extent that it can become the high-affinity site. Placing the high-affinity binding site (Tr4) and the one which can result in familial dysalbuminemic hyperthyroxinemia (Tr1) in two very different parts of HSA is not trivial, because in this way persons with and without the syndrome can have different types of interactions, and thereby complications, when given albumin-bound drugs. The molecular information is also useful when designing drugs based on L-thyroxine analogues. (日)
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| ○キーワード (推奨): | 1. | (英) Binding Sites (日) (読)
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| 2. | (英) Hyperthyroxinemia, Familial Dysalbuminemic (日) (読)
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| 3. | (英) Molecular Docking Simulation (日) (読)
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| 4. | (英) Molecular Dynamics Simulation (日) (読)
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| 5. | (英) Mutation (日) (読)
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| 6. | (英) Serum Albumin (日) (読)
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| 7. | (英) Thyroxine (日) (読)
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| ○発行所 (推奨): |
| ○誌名 (必須): | □ | Biochimica et Biophysica Acta (BBA) - General Subjects ([Elsevier Science])
(pISSN: 0304-4165, eISSN: 1872-8006)
| ○ISSN (任意): | □ | 0304-4165
ISSN: 0304-4165
(pISSN: 0304-4165, eISSN: 1872-8006) Title: Biochimica et biophysica acta. General subjectsTitle(ISO): Biochim Biophys Acta Gen SubjPublisher: Elsevier B.V. (NLM Catalog)
(Scopus)
(CrossRef)
(Scopus information is found. [need login]) | [継承] |
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| ○巻 (必須): | □ | 1860
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| ○号 (必須): | □ | 4
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| ○頁 (必須): | □ | 648 660
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| ○都市 (任意): |
| ○年月日 (必須): | □ | 西暦 2016年 4月 初日 (平成 28年 4月 初日)
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| ○URL (任意): |
| ○DOI (任意): | □ | 10.1016/j.bbagen.2016.01.001 (→Scopusで検索)
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| ○PMID (任意): | □ | 26777880 (→Scopusで検索)
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| ○CRID (任意): |
| ○Scopus (任意): | 1. | 2-s2.0-84963977250
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| ○備考 (任意): | 1. | (英) Article.ELocationID: 10.1016/j.bbagen.2016.01.001 (日)
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| 2. | (英) Article.ELocationID: S0304-4165(16)00002-7 (日)
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| 3. | (英) Article.PublicationTypeList.PublicationType: Journal Article (日)
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| 4. | (英) Article.PublicationTypeList.PublicationType: Research Support, Non-U.S. Gov't (日)
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| 5. | (英) KeywordList.Keyword: Computer modeling (日)
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| 6. | (英) KeywordList.Keyword: Genetic variants (日)
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| 7. | (英) KeywordList.Keyword: High-affinity binding site (日)
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| 8. | (英) KeywordList.Keyword: Human serum albumin (日)
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| 9. | (英) KeywordList.Keyword: L-thyroxine (日)
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| 10. | (英) KeywordList.Keyword: Site-directed mutagenesis (日)
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