Solution structure of human orexin-A: Regulator of appetite and wakefulness

Hai Young Kim, Eunmi Hong, Jae Il Kim, Weontae Lee

Research output: Contribution to journalArticle

22 Citations (Scopus)

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 α-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.

Original languageEnglish
Pages (from-to)565-573
Number of pages9
JournalJournal of Biochemistry and Molecular Biology
Volume37
Issue number5
Publication statusPublished - 2004 Sep 1

Fingerprint

Wakefulness
Appetite
Orexins
Simulated annealing
Drug Design
Disulfides
Nuclear magnetic resonance spectroscopy
Magnetic Resonance Spectroscopy
Eating
Messenger RNA
Peptides
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

Cite this

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Solution structure of human orexin-A : Regulator of appetite and wakefulness. / Kim, Hai Young; Hong, Eunmi; Kim, Jae Il; Lee, Weontae.

In: Journal of Biochemistry and Molecular Biology, Vol. 37, No. 5, 01.09.2004, p. 565-573.

Research output: Contribution to journalArticle

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