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| | ==SOLUTION STRUCTURE OF A HUMAN HYPOCRETIN-2/OREXIN-B'SOLUTION STRUCTURE OF A HUMAN HYPOCRETIN-2/OREXIN-B '== | | ==SOLUTION STRUCTURE OF A HUMAN HYPOCRETIN-2/OREXIN-B'SOLUTION STRUCTURE OF A HUMAN HYPOCRETIN-2/OREXIN-B '== |
| - | <StructureSection load='1cq0' size='340' side='right'caption='[[1cq0]], [[NMR_Ensembles_of_Models | 1 NMR models]]' scene=''> | + | <StructureSection load='1cq0' size='340' side='right'caption='[[1cq0]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| | <table><tr><td colspan='2'>[[1cq0]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CQ0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1CQ0 FirstGlance]. <br> | | <table><tr><td colspan='2'>[[1cq0]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CQ0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1CQ0 FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1cq0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1cq0 OCA], [https://pdbe.org/1cq0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1cq0 RCSB], [https://www.ebi.ac.uk/pdbsum/1cq0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1cq0 ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1cq0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1cq0 OCA], [https://pdbe.org/1cq0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1cq0 RCSB], [https://www.ebi.ac.uk/pdbsum/1cq0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1cq0 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[https://www.uniprot.org/uniprot/OREX_HUMAN OREX_HUMAN]] Defects in HCRT are the cause of narcolepsy type 1 (NRCLP1) [MIM:[https://omim.org/entry/161400 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.<ref>PMID:10973318</ref>
| + | [https://www.uniprot.org/uniprot/OREX_HUMAN OREX_HUMAN] Defects in HCRT are the cause of narcolepsy type 1 (NRCLP1) [MIM:[https://omim.org/entry/161400 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.<ref>PMID:10973318</ref> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/OREX_HUMAN 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.
| + | [https://www.uniprot.org/uniprot/OREX_HUMAN 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. |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | 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, 3JHNalpha coupling constants and hydrogen-deuterium exchange rates together with chemical shift indices, human hypocretin-2/orexin-B was deduced to consist of two alpha-helices connected with a short linker in both H2O and 30% trifluoroethanol solutions. The helical axis of helix I is oriented about 60-80 degrees 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 degrees 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.
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| - | Solution structure of a new hypothalamic neuropeptide, human hypocretin-2/orexin-B.,Lee JH, Bang E, Chae KJ, Kim JY, Lee DW, Lee W Eur J Biochem. 1999 Dec;266(3):831-9. PMID:10583376<ref>PMID:10583376</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 1cq0" style="background-color:#fffaf0;"></div>
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| | ==See Also== | | ==See Also== |
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| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bang, E J]] | + | [[Category: Bang EJ]] |
| - | [[Category: Chae, K J]] | + | [[Category: Chae K-J]] |
| - | [[Category: Lee, D W]] | + | [[Category: Lee DW]] |
| - | [[Category: Lee, K H]] | + | [[Category: Lee K-H]] |
| - | [[Category: Lee, W]] | + | [[Category: Lee W]] |
| - | [[Category: De novo protein]]
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| - | [[Category: Human hcrt-2/ox-b]]
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| - | [[Category: Neuropeptide]]
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| - | [[Category: Obesity]]
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| - | [[Category: Solution structure]]
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| Structural highlights
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.[1]
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.
See Also
References
- ↑ Peyron C, Faraco J, Rogers W, Ripley B, Overeem S, Charnay Y, Nevsimalova S, Aldrich M, Reynolds D, Albin R, Li R, Hungs M, Pedrazzoli M, Padigaru M, Kucherlapati M, Fan J, Maki R, Lammers GJ, Bouras C, Kucherlapati R, Nishino S, Mignot E. A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. Nat Med. 2000 Sep;6(9):991-7. PMID:10973318 doi:10.1038/79690
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