Orexin and Orexin receptor: Difference between revisions
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<StructureSection load='4s0v' size=' | <StructureSection load='4s0v' size='400' side='right' caption='Human orexin receptor complex with insomnia medication belsomra and oleic acid (PDB code [[4s0v]])' scene='77/777976/Cv/1'> | ||
== Function == | == Function == | ||
The '''orexin''' neuropeptides, Orexin-A and Orexin-B, can excite neurons in the brain and affect multiple systems, including the acetylcholine, dopamine, histamine, and norepinephrine systems <ref name="two">doi:10.4088/JCP.13011su1c </ref><ref>PMID:15479620</ref><ref>PMID:10583376</ref>. These orexin neuropeptides bind to two subtypes of '''orexin receptors''', [http://www.rcsb.org/pdb/explore/jmol.do?structureId=4ZJ8&residueNr=SUV Orexin receptor 1] and [http://www.rcsb.org/pdb/explore/jmol.do?structureId=4S0V&residueNr=SUV Orexin receptor 2], both of which are G protein coupled receptors (GPCRs) <ref>doi:10.1038/nsmb.3183</ref>. The GPCRs can sense a molecule outside the cell and send a signal through transduction in order to cause the cells to respond <ref>PMID:9491897 </ref>. Thus, binding of the two can control wakefulness in humans. In studies, Orexin-B has shown to be more selective in binding, choosing to bind to Orexin receptor type 2 a majority of the time. Orexin-A has shown an equal selectivity at both types of receptors <ref name="two" />. | The '''orexin''' neuropeptides, Orexin-A and Orexin-B, can excite neurons in the brain and affect multiple systems, including the acetylcholine, dopamine, histamine, and norepinephrine systems <ref name="two">doi:10.4088/JCP.13011su1c </ref><ref>PMID:15479620</ref><ref>PMID:10583376</ref>. These orexin neuropeptides bind to two subtypes of '''orexin receptors''', [http://www.rcsb.org/pdb/explore/jmol.do?structureId=4ZJ8&residueNr=SUV Orexin receptor 1] and [http://www.rcsb.org/pdb/explore/jmol.do?structureId=4S0V&residueNr=SUV Orexin receptor 2], both of which are [[G protein-coupled receptors]] (GPCRs) <ref>doi:10.1038/nsmb.3183</ref>. The GPCRs can sense a molecule outside the cell and send a signal through transduction in order to cause the cells to respond <ref>PMID:9491897 </ref>. Thus, binding of the two can control wakefulness in humans. In studies, Orexin-B has shown to be more selective in binding, choosing to bind to Orexin receptor type 2 a majority of the time. Orexin-A has shown an equal selectivity at both types of receptors <ref name="two" />. | ||
See also | |||
*[[Hypocretin and receptors]] | |||
*[[Transmembrane (cell surface) receptors]] | |||
== Disease == | == Disease == | ||
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== Structural highlights == | == Structural highlights == | ||
The suvorexant-binding pocket is open to the extracellular space through a constricted solvent-accessible channel. | The <scene name='77/777976/Cv/4'>suvorexant-binding pocket is open to the extracellular space</scene> through a constricted solvent-accessible channel. A <scene name='77/777976/Cv/5'>complex network of electrostatic interactions includes salt bridges between the protein and the drug, on both sides of the entry channel</scene><ref>PMID:25533960</ref>. | ||
See also: | |||
*[[Receptor]] | |||
*[[Transmembrane (cell surface) receptors]] | |||
*[[G protein-coupled receptors]] | |||
</StructureSection> | </StructureSection> | ||
== 3D Structures of orexin and orexin receptor == | == 3D Structures of orexin and orexin receptor == | ||
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*Orexin receptor | *Orexin receptor | ||
**[[4s0v]] – hOrxR- | **[[6tod]] – hOrxR-1 (mutant) + EMPA<br /> | ||
**[[4zj8]], [[4zjc]], [[5wqc]], [[5ws3]] – hOrxR- | **[[6tos]], [[6tq6]], [[6tq7]] – hOrxR-1 (mutant) + pyridine derivative<br /> | ||
**[[6tp4]] – hOrxR-1 (mutant) + pyrrolydine derivative<br /> | |||
**[[6tq4]] – hOrxR-1 (mutant) + benzoxazole derivative<br /> | |||
**[[6tq9]] – hOrxR-1 (mutant) + quinoline derivative<br /> | |||
**[[6tot]], [[6to7]], [[6tp3]], [[6tp6]] – hOrxR-1 (mutant) + insomnia drug<br /> | |||
**[[4s0v]] – hOrxR-1/glycogen synthase + insomnia drug<br /> | |||
**[[4zj8]], [[4zjc]], [[5wqc]], [[5ws3]], [[6tpg]], [[6v9s]] – hOrxR-1/glycogen synthase + antagonist <br /> | |||
**[[7xrr]] – hOrxR-2 + insomnia drug<br /> | |||
**[[7sqoj]], [[7sr8]] – hOrxR-2 + Gi + nanobody + wake-promoting drug – Cryo EM<br /> | |||
**[[6tpj]] – hOrxR-2/glycogen synthase (mutant) + insomnia drug<br /> | |||
**[[6tpn]] – hOrxR-2/glycogen synthase + antagonist <br /> | |||
**[[7l1u]], [[7l1v]] – mOrxR-2 + G protein + nanobody + agonist – Cryo EM<br /> | |||
}} | }} | ||
== References == | == References == | ||
<references/> | <references/> | ||
[[Category:Topic Page]] | [[Category:Topic Page]] | ||