Activity of Artificial Mutant Variants of Human Growth Hormone Changes in Charged Residues around 62-67
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概要
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Our previous work has shown that the amino acid residues around 62-67 located in the connecting loop between helix I and II of human growth hormone (hGH) are important in eliciting the differentiation of preadipose 3T3-F442A cells to adipocytes. In this study, we evaluated the role of the charged residues around 62-67 in receptor binding and biological activity. Eight artificial mutant variants of hGH were prepared in Escherichia coli by site-directed mutagenesis. Replacement of Arg64 with Tyr (R64Y variant) resulted in a significant loss of binding to the somatogenic receptors on 3T3-F442A cells, but retained full adipose conversion activity on these cells. Replacement of Arg64 with Glu (R64E) produced a considerable loss in receptor binding and a significant loss in biological activity. hGH variants in which either Glu65 or Glu66 was replaced with Asp (E65D and E66D) and with Gln (E65Q and E66Q) showed a slight loss in binding activity and retained almost a full adipogenic activity. An E65P variant (replacement of Glu65 with Pro) possessed the same binding activity as hGH, although it failed to induce full biological activity. The insertion of Ala between Asn63 and Arg64 (63NAR) caused a marked loss in both activities. These results indicate that the positively charged Arg64 is important for receptor binding and thereby in eliciting the biological activity of hGH, while negatively charged Glu65 and Glu66 are less important. In addition, our findings confirm that the conformation and size of the loop region around Arg64 is important for the adipose conversion activity of hGH.
- 社団法人日本薬学会の論文
- 1995-06-15
著者
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内田 恵理子
国立医薬品食品衛生研究所遺伝子細胞医薬部
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上杉 晴一
横浜国立大学工学部
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上杉 晴一
Faculty Of Engineering Yokohama National University
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森川 實
Tokyo Institute For Immunopharmacology Inc.
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内田 恵理子
Division of Biological Chemistry and Biologicals, National Institute of Health Sciences
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下川 誠太郎
Faculty of Pharmaceutical Sciences, Osaka University(Present address)
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高須 尚
Faculty of Pharmaceutical Sciences, Osaka University
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池原 森男
Faculty of Pharmaceutical Sciences, Osaka University(Present address)
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冨田 研一
Faculty of Pharmaceutical Sciences, Osaka University
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田中 彰
Division of Biological Chemistry and Biologicals, National Institute of Health Sciences(Present addr
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森川 実
Tokyo Institute for Immunopharmacology, Inc.
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西川 諭
Faculty of Pharmaceutical Sciences, Osaka University
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早川 堯夫
Division of Biological Chemistry and Biologicals, National Institute of Health Sciences
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西川 諭
産総研・生物機能工学
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下川 誠太郎
Faculty Of Pharmaceutical Sciences Osaka University(present Address):yamanouchi Pharmaceutical Co. L
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早川 尭夫
国立医薬品食品衛生研究所
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内田 恵理子
国立衛研
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早川 堯夫
国立医薬品食品衛生研究所生物薬品部
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Morikawa M
Tokyo Institute For Immunopharmacology Inc.
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田中 彰
Division Of Biological Chemistry And Biologicals National Institute Of Health Sciences(present Addre
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冨田 研一
Faculty Of Pharmaceutical Sciences Osaka University
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早川 尭夫
Division Of Biological Chemistry And Reference Standards National Institute Of Hygienic Sciences
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高須 尚
Faculty Of Pharmaceutical Sciences Osaka University
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Tomita K
Faculty Of Pharmaceutical Sciences Osaka University
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Uchida Eriko
Human Genome Center Institute Of Medical Science University Of Tokyo
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上杉 精一
Faculty Of Pharmaceutical Sciences Osaka University
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池原 森男
Faculty Of Pharmaceutical Sciences Osaka University
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西川 諭
Faculty Of Pharmaceutical Sciences Osaka University
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上杉 晴一
Faculty Of Pharmaceutical Sciences Osaka University
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