Solution structure of a new hypothalamic neuropeptide, human hypocretin- 2/orexin-B

Jung Hoon Lee, Eunjung Bang, Kyeong Jun Chae, Jin Young Kim, Dai Woon Lee, Weon Tae Lee

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Orexin-A and orexin-B (also called hypocretin-1 and hypocretin-2, respectively) are novel hypothalamic neuropeptides encoded by a single mRNA transcript; they stimulate food intake. We have determined the three- dimensional solution structure of human hypocretin-2/orexin-B using two- dimensional 1H-NMR data and dynamical simulated annealing calculations. On the basis of NOEs, 3J(NHα) coupling constants and hydrogen-deuterium exchange rates together with chemical shift indices, human hypocretin- 2/orexin-B was deduced to consist of two α-helices connected with a short linker in both H2O and 30% trifluoroethanol solutions. The helical axis of helix I is oriented about 60-80°relative to helix II. Hybrid distance geometry and simulated-annealing protocols were used to generate an ensemble of 30 structures with no constraint violations greater than 0.03 nm for distances and 3°for angles. In addition, human hypocretin-2/orexin-B shares a similar secondary-structural motif with human neuropeptide Y. This result can form the basis for further study on ligand-receptor recognition of human orexin receptors.

Original languageEnglish
Pages (from-to)831-839
Number of pages9
JournalEuropean Journal of Biochemistry
Volume266
Issue number3
DOIs
Publication statusPublished - 1999 Dec 15

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Neuropeptides
Simulated annealing
Orexin Receptors
Orexins
Trifluoroethanol
Deuterium
Neuropeptide Y
Chemical shift
Hydrogen
Eating
Nuclear magnetic resonance
Ligands
Messenger RNA
Geometry

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Lee, Jung Hoon ; Bang, Eunjung ; Chae, Kyeong Jun ; Kim, Jin Young ; Lee, Dai Woon ; Lee, Weon Tae. / Solution structure of a new hypothalamic neuropeptide, human hypocretin- 2/orexin-B. In: European Journal of Biochemistry. 1999 ; Vol. 266, No. 3. pp. 831-839.
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Solution structure of a new hypothalamic neuropeptide, human hypocretin- 2/orexin-B. / Lee, Jung Hoon; Bang, Eunjung; Chae, Kyeong Jun; Kim, Jin Young; Lee, Dai Woon; Lee, Weon Tae.

In: European Journal of Biochemistry, Vol. 266, No. 3, 15.12.1999, p. 831-839.

Research output: Contribution to journalArticle

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