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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Solution Structure of Human Orexin-A: Regulator of Appetite and Wakefulness

  • Kim, Hai-Young (Department of Biochemistry, College of Science, Yonsei University) ;
  • Hong, Eun-Mi (Department of Biochemistry, College of Science, Yonsei University) ;
  • Kim, Jae-Il (Anygen Co.) ;
  • Lee, Weon-Tae (Department of Biochemistry, College of Science, Yonsei University)
  • Published : 2004.09.30
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Abstract

Orexin-A and orexin-B (hypocretin-1 and hypocretin-2, respectively) are important hypothalamic neuro-peptides, which are encoded by a single mRNA transcript and stimulate food intake as well as regulate wakefulness. Here we determined the solution structure of orexin-A by NMR spectroscopy and by simulated-annealing calculation. The structural features of orexin-A involve two $\alpha$-helices, with the hydrophobic residues disposed to on one side of helix, and hydrophilic residues to the other. A hydrophilic turn induced by two disulfide bonds provides the key difference between orexin-A and -B. With previous mutagenic studies, the derived structure of orexin-A provides us with a structure-functional view for novel drug design.

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