Modeling of the OX1R–orexin-A complex suggests two alternative binding modes

Karhu, Lasse; Turku, Ainoleena; Xhaard, Henri

doi:10.1186/s12900-015-0036-2

BMC Structural Biology

Table 1 Binding interactions of the two presented binding modes

From: Modeling of the OX₁R–orexin-A complex suggests two alternative binding modes

Ligand residue	Interactions with receptor residues
Ligand residue	TM7-mode	TM5-mode
Leu16	Alkyl - Val188^xl2.36, Glu191^xl2.39	-
Tyr17	Aromatic - Phe199^xl2.47	Alkyl-π - Met326^6.63
Glu18	Salt bridge - Arg333^7.28, Lys43^1.29	Salt bridge - Arg322^6.59
Glu18	H-bond - Tyr41^1.27 (backbone N)	Salt bridge - Arg322^6.59
Leu19	CH–O to backbone - Arg333^7.28	-
Leu20	-	-
His21	Aromatic - Phe199xl^2.47	H-bond - Arg333^7.28
	Alkyl-π - Val201^xl2.49	Cation-π - Arg328^6.65
	H-bond - Glu110^2.68 (backbone carbonyl)	Alkyl-π - Met326^6.63
	H-bond - Glu110^2.68 (backbone carbonyl)	H-bond to backbone - Arg322^6.59
Gly22	-	-
Ala23	Alkyl - Arg333^7.28	Alkyl - Arg205^xl2.53
Ala23	H-bond to backbone - Lys321^6.58	Alkyl - Arg205^xl2.53
Gly24	-	CH–O hydrogen bond - Asp203 ^xl2.51
Asn25	H-bond - Cys202^xl2.50 (backbone nitrogen)	H-bond - Arg328^6.65, Lys321^6.58 (putative)
Asn25	H-bond - Cys202^xl2.50 (backbone nitrogen)	H-bond to backbone - Glu204^xl2.52, Lys321^6.58 (conventional or CH–O)
His26	Aromatic - Tyr337^7.32, Phe340^7.35	Alkyl-π - Arg322^6.59, Val182^4.63, Pro212^5.35
	CH–O hydrogen bond - Asp107^2.65	H-bond - Glu204^xl2.52
	CH–O hydrogen bond - Asp107^2.65	CH–O hydrogen bond - Pro212^5.35 (carbonyl)
Ala27	Alkyl - Lys321^6.58	Alkyl - Met183^4.64
Ala28	Alkyl - Met183^4.64	-
Ala28	H-bond to backbone - Asp203 ^xl2.51	-
Gly29	-	H-bond to backbone - Asn318 ^6.55 (requires rotamer change)
Ile30	Alkyl-π - Phe340^7.35, His344 ^7.39	Alkyl - Pro123^3.29
	Alkyl - Ile314^6.51, Ser323^7.38	H-bond to backbone - Gln126 ^3.32
	H-bond to backbone - Asn318 ^6.55	H-bond to backbone - Gln126 ^3.32
Leu31	Alkyl-π - Tyr215 ^5.37, His216^5.39	Alkyl-π - Trp112^xl1.50
	Lone pair-π from backbone - Phe219 ^5.42	Alky - Ile122^3.28, Pro123^3.29
		H-bond to backbone - Ser103^2.61
		CH–O hydrogen bond to backbone - His344 ^7.39
Thr32	H-bond - Gln179^4.60, Pro123^3.29 (backbone carbonyl)	Alkyl-π - Phe340^7.35, His344 ^7.39
		Alkyl - Ile314^6.51
		H-bond - Ser343^7.38, His344 ^7.39 (either to threonine hydroxyl or backbone carbonyl)
Leu33	Alkyl-π - His344 ^7.39, Tyr348 ^7.43	Alkyl-π - Phe219 ^5.42
	Alkyl - Ile314^6.51, Val347^7.42	Alkyl - Ile314^6.51
	H-bond to backbone - Gln126 ^3.32	Alkyl - Ile314^6.51
NH2	H-bond - Tyr311 ^6.48 (requires rotamer change)	Close to Gln126 ^3.32 (unfavorable geometry for H-bond)

Interactions divided by type. Unless otherwise noted, the interacting atoms are side-chain atoms. “Requires rotamer change” denotes putative interactions which would take place if a receptor residue adopted a slightly different rotamer. Receptor residues whose mutation has been shown to be detrimental to orexin peptide binding are in bold.

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ISSN: 1472-6807

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