Peptide Helix-Y¹² as Potential Effector for Peroxisome Proliferator-Activated Receptors

Table 2

Main characteristics of Helix-Y¹² interaction with PPARs.

	PPARα	PPARβ/δ	PPARγ
∆Gb	−8.9	−7.9	−8.0
Interaction with Y-shaped ligand-binding pocket	Arm I, II, III^a, and X	Arm I, II, III and X^a	Arm I, II, III^a, and X
Amino acid residues involved in H-bond (Receptor Helix-Y^12)	Tyr314^b–Cys1	Asn343–Leu8	Ser289^b–Cys1
	Tyr464^b–Cys1	Asn343–Gln9	Ile262–Val5
	Ala250–Ser10	Lys265–Ser10	Lys275–Leu8
		Arg284–Ser10 (2x)	Lys275–Gln9
			Ser464–Gln9
Hydrophobic contacts (mainly)	H3 (30%)	H3 (29%)	H3 (37%)
	H2′ (13.3%)	H5 (14%)	H5 (15%)
	H2′–H3 loop (13.3%)	H2′–H3 (11%)	H12 (11%)
	β2/β3 loop (10%)	H7 (11%)	H11–H12 (11%)
Advantages	Stablish two hydrogen bonds with residues of helix H12 important to LBD stabilization.	Hydrogen bonds are in Arm II and entrance.	Clamp surrounds H3, contacts with H12through a H-bond and several hydrophobic interactions, reaching loop H11–H12 from outside.

^aPartial contact.
^bPreviously reported amino acids interacting with endogenous/exogenous ligands.