title: Fine-tuned broad binding capability of human lipocalin-type prostaglandin D synthase for various small lipophilic ligands.
abstract: The hydrophobic cavity of lipocalin-type prostaglandin D synthase (L-PGDS) has been suggested to accommodate various lipophilic ligands through hydrophobic effects, but its energetic origin remains unknown. We characterized 18 buffer-independent binding systems between human L-PGDS and lipophilic ligands using isothermal titration calorimetry. Although the classical hydrophobic effect was mostly detected, all complex formations were driven by favorable enthalpic gains. Gibbs energy changes strongly correlated with the number of hydrogen bond acceptors of ligand. Thus, the broad binding capability of L-PGDS for ligands should be viewed as hydrophilic interactions delicately tuned by enthalpy-entropy compensation using combined effects of hydrophilic and hydrophobic interactions.
authors: Laboratory of Biological Macromolecules, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan; Cellular Function Imaging Team, Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technologies, 6-7-3, Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors: Satoshi
authors: S
authors: Kume
authors: Institute for Protein Research, Osaka University, Yamadaoka 3-2, Suita, Osaka 565-0871, Japan.
authors: Young-Ho
authors: YH
authors: Lee
authors: Laboratory of Biological Macromolecules, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.
authors: Masatoshi
authors: M
authors: Nakatsuji
authors: Laboratory of Biological Macromolecules, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.
authors: Yoshiaki
authors: Y
authors: Teraoka
authors: Laboratory of Biological Macromolecules, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.
authors: Keisuke
authors: K
authors: Yamaguchi
authors: Institute for Protein Research, Osaka University, Yamadaoka 3-2, Suita, Osaka 565-0871, Japan.
authors: Yuji
authors: Y
authors: Goto
authors: Laboratory of Biological Macromolecules, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan. Electronic address: inuit@bioinfo.osakafu-u.ac.jp.
authors: Takashi
authors: T
authors: Inui
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000737:chemistry; D019943:Amino Acid Substitution; D001663:Bilirubin / Q000737:chemistry; D001664:Biliverdine / Q000737:chemistry; D020134:Catalytic Domain; D042341:Gonadal Hormones / Q000737:chemistry; D006427:Hemin / Q000737:chemistry; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D019746:Intramolecular Oxidoreductases / Q000737:chemistry* / Q000235:genetics; D008024:Ligands; D054834:Lipocalins / Q000737:chemistry* / Q000235:genetics; D009282:Naphthalenesulfonates / Q000737:chemistry; D011485:Protein Binding; D013256:Steroids / Q000737:chemistry; D013816:Thermodynamics; D013963:Thyroid Hormones / Q000737:chemistry; D014212:Tretinoin / Q000737:chemistry
chemical_list: D042341:Gonadal Hormones; D008024:Ligands; D054834:Lipocalins; D009282:Naphthalenesulfonates; D013256:Steroids; D013963:Thyroid Hormones; D014212:Tretinoin; D006427:Hemin; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C009497:2-(4-toluidino)-6-naphthalenesulfonic acid; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D001664:Biliverdine; D001663:Bilirubin
keywords: Binding thermodynamic; Driving force; Enthalpy–entropy compensation; Hydrophobic effect; Isothermal titration calorimetry; Lipocalin-type prostaglandin D synthase; Protein–ligand interaction