6TPJ: Orexin-2 receptor

Crystal structure of the Orexin-2 receptor in complex with suvorexant at 2.76 A resolution. Determined by X-ray diffraction at 2.74 Å resolution. Released 1 Jan 2020.

Method: X-ray diffraction
Resolution: 2.74 Å
Organisms: Homo sapiens, Pyrococcus abyssi GE5
Chains: 2
Atoms: 8,578
Mol. weight: 140.02 kDa
Ligands: OLA, SUV
Released: 1 Jan 2020

Explore 6TPJ in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

6TPJ contains 50 α-helices and 20 β-strands across 2 chains. Residue ranges use author residue numbering, as in the PDB file, from PDBe. To see them in 3D, choose the Cartoon representation with Secondary structure coloring: helices, sheets and coils get different colors.

Chain A: 25 helices, 10 β-strands

Element	Residues	Length	Sheet
α-helix	54-81	28
α-helix	83-85	3
α-helix	88-106	19
α-helix	108-117	10
α-helix	123-156	34
α-helix	166-183	18
α-helix	185-190	6
β-strand	191-196	6	1
β-strand	207-212	6	1
α-helix	218-228	11
α-helix	229-233	5
α-helix	234-247	14
α-helix	248-252	5
α-helix	1009-1011	3
α-helix	1016-1026	11
β-strand	1033-1038	6	2
β-strand	1041	1	3
α-helix	1048-1059	12
α-helix	1062-1066	5
β-strand	1067-1072	6	2
β-strand	1075	1	3
α-helix	1077-1089	13
β-strand	1093-1096	4	2
α-helix	1102-1111	10
β-strand	1114-1117	4	2
α-helix	1126-1133	8
α-helix	1136	1
β-strand	1137-1141	5	2
α-helix	1144-1149	6
β-strand	1156-1158	3	2
α-helix	1163-1177	15
α-helix	1182-328	50
α-helix	339-367	29
α-helix	369-379	11
α-helix	380-384	5

Chain B: 25 helices, 10 β-strands

Element	Residues	Length	Sheet
α-helix	54-81	28
α-helix	83-85	3
α-helix	88-106	19
α-helix	108-117	10
α-helix	123-156	34
α-helix	166-183	18
α-helix	185-190	6
β-strand	191-196	6	4
β-strand	207-212	6	4
α-helix	218-228	11
α-helix	229-233	5
α-helix	234-247	14
α-helix	248-252	5
α-helix	1009-1011	3
α-helix	1016-1026	11
β-strand	1033-1038	6	5
β-strand	1041	1	6
α-helix	1048-1059	12
α-helix	1062-1066	5
β-strand	1067-1072	6	5
β-strand	1075	1	6
α-helix	1077-1089	13
β-strand	1093-1096	4	5
α-helix	1102-1109	8
β-strand	1114-1117	4	5
α-helix	1126-1133	8
α-helix	1136	1
β-strand	1137-1141	5	5
α-helix	1144-1149	6
β-strand	1156-1158	3	5
α-helix	1163-1176	14
α-helix	1182-328	50
α-helix	340-367	28
α-helix	369-379	11
α-helix	380-384	5

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Orexin receptor type 2,GlgA glycogen synthase,Hypocretin receptor-2	A, B	protein	564	Homo sapiens, Pyrococcus abyssi GE5	O43614 (AlphaFold model), Q9V2J8 (AlphaFold model)

Sequence of entity 1 (A, B), FASTA

>6TPJ_1 Orexin receptor type 2,GlgA glycogen synthase,Hypocretin receptor-2 (chains A, B)
QDLDYKDDDDKMSGTKLEDSPPCRDWSSASELDETQEPLLDPTDYDDEEFLRYLWREYLH
PKEYAWVLIAGYIIVFVVALIGNVLVCVAVWKNHHMRTVTNLFIVNLSLAAVLVTITCLP
ATLVVDITETWFFGQSLCKVIPYLQTVSVSVSALTLSCIALDRWYAICHPLMFKSTAKRA
LNSIVIIWIVSCIIMIPQAIVMECSTVFPGLADKTTAFTVCDERWGGEIAPKMYHICFFL
VTYAAPLCLMVLLYLQIFRKLWCRQGIDCSFWNESYLTGSRDERKKSLLSKFGMDEGVTF
MFIGRFDRGQKGVDVLLKAIEILSSKKEFQEMRFIIIGKGDPELEGWARSLEEKHGNVKV
ITEMLSREFVRELYGSVDFVIIPSYFEPFGLVALEAMCLGAIPIASAVGGLRDIITNETG
ILVKAGDPGELANAILKALELSRSDLSKFRENCKKRAMSFSKQIRARRKTARMLMVVVLV
FAICYAPISILNVLKRVFGMFAHTEDRETVYAWFAFSHWLVYANSAANPIIYNFLSGKFR
EEFKAAFSWWWLGVHHHHHHHHHH

Ligands and cofactors

ID	Name	Formula	Copies
OLA	Oleic acid	C18 H34 O2	34
SUV	[(7R)-4-(5-chloro-1,3-benzoxazol-2-yl)-7-methyl-1,4-diazepan-1-yl][5-methyl-2-(…	C23 H23 Cl N6 O2	2

Water and common crystallization additives (NH4, PG4) are not listed.

Primary citation

Comparison of Orexin 1 and Orexin 2 Ligand Binding Modes Using X-ray Crystallography and Computational Analysis. Rappas, M., Ali, A.A.E., Bennett, K.A. et al. J Med Chem (2020) 63:1528-1543. DOI 10.1021/acs.jmedchem.9b01787 · PubMed

Other PDB entries of the same protein (UniProt O43614 (AlphaFold model), which also has an AlphaFold model), best resolution first:

5WQC 1.96 Å, Crystal structure of human orexin 2 receptor bound to the selective antagonist EMPA…
5WS3 2.3 Å, Crystal structures of human orexin 2 receptor bound to the selective antagonist EMPA…
4S0V 2.5 Å, Crystal structure of the human OX2 orexin receptor bound to the insomnia drug Suvorexant
6TPN 2.61 Å, Crystal structure of the Orexin-2 receptor in complex with HTL6641 at 2.61 A resolution
6TPG 2.74 Å, Crystal structure of the Orexin-2 receptor in complex with EMPA at 2.74 A resolution
7XRR 2.89 Å, Crystal structure of the human OX2R bound to the insomnia drug lemborexant.
7L1V 3.0 Å, Orexin Receptor 2 (OX2R) in Complex with G Protein and Small-Molecule Agonist Compound 1
7SQO 3.17 Å, Structure of the orexin-2 receptor(OX2R) bound to TAK-925, Gi and scFv16
7L1U 3.2 Å, Orexin Receptor 2 (OX2R) in Complex with G Protein and Natural Peptide-Agonist Orexin B…
21CI 3.29 Å, Crystal structure of human orexin type 2 receptor in complex with vornorexant
7SR8 3.3 Å, Molecular mechanism of the the wake-promoting agent TAK-925

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