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タイトル
  • en Structure of Pleiotrophin- and Hepatocyte Growth Factor-binding Sulfated Hexasaccharide Determined by Biochemical and Computational Approaches
作成者
    • en Li, Fuchuan
    • en Nandini, Chilkunda D.
    • en Hattori, Tomohide
    • en Bao, Xingfeng
    • en Murayama, Daisuke
    • en Nakamura, Toshikazu
    • en Fukushima, Nobuhiro
アクセス権 open access
主題
  • NDC 460
内容注記
  • Abstract en Endogenous pleiotrophin and hepatocyte growth factor (HGF) mediate the neurite outgrowth-promoting activity of chondroitin sulfate (CS)/dermatan sulfate (DS) hybrid chains isolated from embryonic pig brain. CS/DS hybrid chains isolated from shark skin have a different disaccharide composition, but also display these activities. In this study, pleiotrophin- and HGF-binding domains in shark skin CS/DS were investigated. A high-affinity CS/DS fraction was isolated using a pleiotrophin-immobilized column. It showed marked neurite outgrowth-promoting activity and strong inhibitory activity against the binding of pleiotrophin to immobilized CS/DS chains from embryonic pig brain. The inhibitory activity was abolished by chondroitinase ABC or B, and partially reduced by chondroitinase AC-I. A pentasulfated hexasaccharide with a novel structure was isolated from the chondroitinase AC-I digest using pleiotrophin-affinity and anion-exchange chromatographies. It displayed a potent inhibitory effect on the binding of HGF to immobilized shark skin CS/DS chains, suggesting that the pleiotrophin- and HGF-binding domains at least partially overlap in the CS/DS chains involved in the neuritogenic activity. Computational chemistry using molecular modeling and calculations of the electrostatic potential of the hexasaccharide and two pleiotrophin-binding octasaccharides previously isolated from CS/DS hybrid chains of embryonic pig brain identified an electronegative zone potentially involved in the molecular recognition of the oligosaccharides by pleiotrophin. Homology modeling of pleiotrophin based on a related midkine protein structure predicted the binding pocket of pleiotrophin for the oligosaccharides and provided new insights into the molecular mechanism of the interactions between the oligosaccharides and pleiotrophin.
日付
    Issued2010-09-03
言語
  • eng
資源タイプ journal article
出版タイプ AM
資源識別子 HDL http://hdl.handle.net/2115/44207
関連
  • isVersionOf DOI https://doi.org/10.1074/jbc.M110.118703
  • PMID 20584902
収録誌情報
    • PISSN 0021-9258
      • en Journal of Biological Chemistry
      • 285 36 開始ページ27673 終了ページ27685
ファイル
コンテンツ更新日時 2023-07-26