6TOD
Crystal structure of the Orexin-1 receptor in complex with EMPA
Summary for 6TOD
| Entry DOI | 10.2210/pdb6tod/pdb |
| Related | 6TO7 |
| Descriptor | Orexin receptor type 1, N-ethyl-2-[(6-methoxypyridin-3-yl)-(2-methylphenyl)sulfonyl-amino]-N-(pyridin-3-ylmethyl)ethanamide, SULFATE ION, ... (9 entities in total) |
| Functional Keywords | 7tm, gpcr, membrane protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 94726.68 |
| 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. (deposition date: 2019-12-11, release date: 2020-01-01, Last modification date: 2024-10-23) |
| Primary citation | Rappas, M.,Ali, A.A.E.,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. J.Med.Chem., 63:1528-1543, 2020 Cited by PubMed Abstract: The orexin system, which consists of the two G protein-coupled receptors OX and OX, activated by the neuropeptides OX-A and OX-B, is firmly established as a key regulator of behavioral 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 10 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 OX and OX can be achieved are discussed. PubMed: 31860301DOI: 10.1021/acs.jmedchem.9b01787 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.11 Å) |
Structure validation
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