Solution structure of human orexin-A: regulator of appetite and wakefulness.
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Kim HY, Hong E, Kim JI, Lee W
Solution structure of human orexin-A: regulator of appetite and wakefulness.
J Biochem Mol Biol. 2004 Sep 30;37(5):565-73.
- PubMed ID
- 15479620 [ View in PubMed]
- 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.