Solution structure of human orexin-A: regulator of appetite and wakefulness.
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.
Department of Biochemistry, College of Science, Yonsei University, Seoul 120-740, Korea.
Hai-Young
HY
Kim
Eunmi
E
Hong
Jae-Il
JI
Kim
Weontae
W
Lee
D001066:Appetite / Q000502:physiology*; D002942:Circular Dichroism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000502:physiology; D009682:Magnetic Resonance Spectroscopy; D009479:Neuropeptides / Q000737:chemistry* / Q000502:physiology; D000068797:Orexins; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship; D014851:Wakefulness / Q000502:physiology*
C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins