1r02

Solution structure of Human Orexin-A:Regulator of Appetite and WakefulnessSolution structure of Human Orexin-A:Regulator of Appetite and Wakefulness

Structural highlights 1r02 is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR, 1 model Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease OREX_HUMAN Defects in HCRT are the cause of narcolepsy type 1 (NRCLP1) [MIM:161400. Narcolepsy is a neurological disabling sleep disorder, characterized by excessive daytime sleepiness, sleep fragmentation, symptoms of abnormal rapid-eye-movement (REM) sleep, such as cataplexy, hypnagogic hallucinations, and sleep paralysis. Cataplexy is a sudden loss of muscle tone triggered by emotions, which is the most valuable clinical feature used to diagnose narcolepsy. Human narcolepsy is primarily a sporadically occurring disorder but familial clustering has been observed. Note=Human narcolepsy is associated with a deficient orexin system. Orexins are absent and/or greatly diminished in the brain and cerebrospinal fluid (CSF) of most narcoleptic patients. Function OREX_HUMAN Neuropeptides that play a significant role in the regulation of food intake and sleep-wakefulness, possibly by coordinating the complex behavioral and physiologic responses of these complementary homeostatic functions. A broader role in the homeostatic regulation of energy metabolism, autonomic function, hormonal balance and the regulation of body fluids, is also suggested. Orexin-A binds to both OX1R and OX2R with a high affinity, whereas orexin-B binds only to OX2R with a similar high affinity. Publication Abstract from PubMed 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. Solution structure of human orexin-A: regulator of appetite and wakefulness.,Kim HY, Hong E, Kim JI, Lee W J Biochem Mol Biol. 2004 Sep 30;37(5):565-73. PMID:15479620 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Orexin and Orexin receptor

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