6tot: Difference between revisions

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-'''Unreleased structure'''
-The entry 6tot is ON HOLD  until sometime in the future
+==Crystal structure of the Orexin-1 receptor in complex with lemborexant==
+<StructureSection load='6tot' size='340' side='right'caption='[[6tot]], [[Resolution|resolution]] 2.22&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6tot]] 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=6TOT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6TOT FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NRK:(1~{R},2~{S})-2-[(2,4-dimethylpyrimidin-5-yl)oxymethyl]-~{N}-(5-fluoranylpyridin-2-yl)-2-(3-fluorophenyl)cyclopropane-1-carboxamide'>NRK</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</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">[[6tod|6tod]], [[6tos|6tos]], [[6to7|6to7]]</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=6tot FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tot OCA], [http://pdbe.org/6tot PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6tot RCSB], [http://www.ebi.ac.uk/pdbsum/6tot PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6tot ProSAT]</span></td></tr>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/OX1R_HUMAN 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).
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The 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.
-Authors: Rappas, M., Ali, A., Bennett, K.A., Brown, J.D., Bucknell, S.J., Congreve, M., Cooke, R.M., Cseke, G., de Graaf, C., Dore, A.S., Errey, J.C., Jazayeri, A., Marshall, F.H., Mason, J.S., Mould, R., Patel, J.C., Tehan, B.G., Weir, M., Christopher, J.A.
+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<ref>PMID:31860301</ref>
-Description: Crystal structure of the Orexin-1 receptor in complex with lemborexant
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Weir, M]]
+<div class="pdbe-citations 6tot" style="background-color:#fffaf0;"></div>
-[[Category: Tehan, B.G]]
+== References ==
-[[Category: Christopher, J.A]]
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
+[[Category: Ali, A]]
+[[Category: Bennett, K A]]
+[[Category: Brown, J D]]
+[[Category: Bucknell, S J]]
+[[Category: Christopher, J A]]
 [[Category: Congreve, M]]
-[[Category: Mason, J.S]]
+[[Category: Cooke, R M]]
+[[Category: Cseke, G]]
+[[Category: Dore, A S]]
+[[Category: Errey, J C]]
+[[Category: Graaf, C de]]
 [[Category: Jazayeri, A]]
-[[Category: Bucknell, S.J]]
+[[Category: Marshall, F H]]
-[[Category: Cseke, G]]
+[[Category: Mason, J S]]
-[[Category: Marshall, F.H]]
-[[Category: Cooke, R.M]]
 [[Category: Mould, R]]
-[[Category: Brown, J.D]]
+[[Category: Patel, J C]]
-[[Category: Patel, J.C]]
-[[Category: Errey, J.C]]
-[[Category: De Graaf, C]]
 [[Category: Rappas, M]]
-[[Category: Ali, A]]
+[[Category: Tehan, B G]]
-[[Category: Dore, A.S]]
+[[Category: Weir, M]]
-[[Category: Bennett, K.A]]
+[[Category: Gpcr]]
+[[Category: Membrane protein]]