6tq4: Difference between revisions
No edit summary |
No edit summary |
||
| Line 3: | Line 3: | ||
<StructureSection load='6tq4' size='340' side='right'caption='[[6tq4]], [[Resolution|resolution]] 2.30Å' scene=''> | <StructureSection load='6tq4' size='340' side='right'caption='[[6tq4]], [[Resolution|resolution]] 2.30Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6tq4]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TQ4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6TQ4 FirstGlance]. <br> | <table><tr><td colspan='2'>[[6tq4]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TQ4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6TQ4 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NV8:2-[1-(phenylsulfonyl)-1,8-diazaspiro[4.5]decan-8-yl]-1,3-benzoxazole'>NV8</scene>, <scene name='pdbligand=PGW:(1R)-2-{[(S)-{[(2S)-2,3-DIHYDROXYPROPYL]OXY}(HYDROXY)PHOSPHORYL]OXY}-1-[(HEXADECANOYLOXY)METHYL]ETHYL+(9Z)-OCTADEC-9-ENOATE'>PGW</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=SOG:2-HYDROXYMETHYL-6-OCTYLSULFANYL-TETRAHYDRO-PYRAN-3,4,5-TRIOL'>SOG</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NV8:2-[1-(phenylsulfonyl)-1,8-diazaspiro[4.5]decan-8-yl]-1,3-benzoxazole'>NV8</scene>, <scene name='pdbligand=PGW:(1R)-2-{[(S)-{[(2S)-2,3-DIHYDROXYPROPYL]OXY}(HYDROXY)PHOSPHORYL]OXY}-1-[(HEXADECANOYLOXY)METHYL]ETHYL+(9Z)-OCTADEC-9-ENOATE'>PGW</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=SOG:2-HYDROXYMETHYL-6-OCTYLSULFANYL-TETRAHYDRO-PYRAN-3,4,5-TRIOL'>SOG</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6to7|6to7]], [[6tod|6tod]], [[6tos|6tos]], [[6tot|6tot]], [[6tp6|6tp6]], [[6tp3|6tp3]], [[6tp4|6tp4]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6to7|6to7]], [[6tod|6tod]], [[6tos|6tos]], [[6tot|6tot]], [[6tp6|6tp6]], [[6tp3|6tp3]], [[6tp4|6tp4]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HCRTR1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6tq4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tq4 OCA], [http://pdbe.org/6tq4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6tq4 RCSB], [http://www.ebi.ac.uk/pdbsum/6tq4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6tq4 ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6tq4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tq4 OCA], [http://pdbe.org/6tq4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6tq4 RCSB], [http://www.ebi.ac.uk/pdbsum/6tq4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6tq4 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| Line 23: | Line 24: | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Ali, A]] | [[Category: Ali, A]] | ||
Revision as of 19:24, 29 January 2020
Crystal structure of the Orexin-1 receptor in complex with Compound 16Crystal structure of the Orexin-1 receptor in complex with Compound 16
Structural highlights
Function[OX1R_HUMAN] Moderately selective excitatory receptor for orexin-A and, with a lower affinity, for orexin-B neuropeptide. Seems to be exclusively coupled to the G(q) subclass of heteromeric G proteins, which activates the phospholipase C mediated signaling cascade (By similarity). Publication Abstract from PubMedThe orexin system, which consists of the two G protein-coupled receptors OX1 and OX2, activated by the neuropeptides OX-A and OX-B, is firmly established as a key regulator of behavioural arousal, sleep and wakefulness, and has been an area of intense research effort over the past two decades. X-ray structures of the receptors in complex with ten new antagonist ligands from diverse chemotypes are presented, which complement the existing structural information for the system and highlight the critical importance of lipophilic hotspots and water molecules for these peptidergic GPCR targets. Learnings from the structural information regarding the utility of pharmacophore models and how selectivity between OX1 and OX2 can be achieved are discussed. Comparison of orexin 1 and orexin 2 ligand binding modes using X-ray crystallography and computational analysis.,Rappas M, Ali A, Bennett KA, Brown JD, Bucknell SJ, Congreve M, Cooke RM, Cseke G, de Graaf C, Dore AS, Errey JC, Jazayeri A, Marshall FH, Mason JS, Mould R, Patel JC, Tehan B, Weir M, Christopher JA J Med Chem. 2019 Dec 20. doi: 10.1021/acs.jmedchem.9b01787. PMID:31860301[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||||||