1r02 Citations

Solution structure of human orexin-A: regulator of appetite and wakefulness.

J Biochem Mol Biol 37 565-73 (2004)
Cited: 18 times
EuropePMC logo PMID: 15479620

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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Reviews citing this publication (8)

  1. Orexin neuronal circuitry: role in the regulation of sleep and wakefulness. Ohno K, Sakurai T. Front Neuroendocrinol 29 70-87 (2008)
  2. The hypothalamic orexinergic system: pain and primary headaches. Holland P, Goadsby PJ. Headache 47 951-962 (2007)
  3. Physiology of the orexinergic/hypocretinergic system: a revisit in 2012. Kukkonen JP. Am J Physiol Cell Physiol 304 C2-32 (2013)
  4. Migraine and neuropeptides. Tajti J, Szok D, Majláth Z, Tuka B, Csáti A, Vécsei L. Neuropeptides 52 19-30 (2015)
  5. Challenges in the development of therapeutics for narcolepsy. Black SW, Yamanaka A, Kilduff TS. Prog Neurobiol 152 89-113 (2017)
  6. An overview of hypocretin based therapy in narcolepsy. Takenoshita S, Sakai N, Chiba Y, Matsumura M, Yamaguchi M, Nishino S. Expert Opin Investig Drugs 27 389-406 (2018)
  7. The Human Orexin/Hypocretin Receptor Crystal Structures. Yin J, Rosenbaum DM. Curr Top Behav Neurosci 33 1-15 (2017)
  8. Understanding the Biological Relationship between Migraine and Depression. Viudez-Martínez A, Torregrosa AB, Navarrete F, García-Gutiérrez MS. Biomolecules 14 163 (2024)

Articles citing this publication (9)