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PDBsum entry 6tpj
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Membrane protein
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PDB id
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6tpj
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References listed in PDB file
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Key reference
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Title
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Comparison of orexin 1 and orexin 2 ligand binding modes using x-Ray crystallography and computational analysis.
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Authors
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M.Rappas,
A.A.E.Ali,
K.A.Bennett,
J.D.Brown,
S.J.Bucknell,
M.Congreve,
R.M.Cooke,
G.Cseke,
C.De graaf,
A.S.Doré,
J.C.Errey,
A.Jazayeri,
F.H.Marshall,
J.S.Mason,
R.Mould,
J.C.Patel,
B.G.Tehan,
M.Weir,
J.A.Christopher.
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Ref.
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J Med Chem, 2020,
63,
1528-1543.
[DOI no: ]
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PubMed id
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Abstract
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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 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 OX1 and OX2 can be
achieved are discussed.
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