Orexin and Orexin receptor: Difference between revisions

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 suvorexant-binding pocket is open to the extracellular space through a constricted solvent-accessible channel. A complex network of electrostatic interactions includes salt bridges between the protein and the drug, on both sides of the entry channel<ref>PMID:25533960</ref>.  

**[[4s0v]] – hOrxR-A/glycogen synthase + Suvorexant <br />

**[[4zj8]], [[4zjc]], [[5wqc]], [[5ws3]] – hOrxR-A/glycogen synthase + antagonist <br />