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evolution
the enzyme belongs to the lipocalin superfamily
evolution
the enzyme is a member of the lipocalin superfamily
malfunction
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co-localization of arrestin-3 with L-PGDS is drastically reduced in MG-63 cells when L-PGDS activity is inhibited
malfunction
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dextran sodium sulfate treatment to L-PGDS-deficientmice shows lower ulcerative colitis disease activity than control mice
malfunction
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the stable transfection with antisense L-PGDS induces markedly the stimulation of fat storage in cultured adipocytes during the maturation phase
malfunction
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double knockout mice, lacking lipocalin prostaglandin D synthase as well as PPARgamma2, have impaired carbohydrate and lipid metabolism with glucose tolerance compared to any other genotypes, their interscapular brown adipose tissue exhibits greater lipid content than that of wild-type mice, which is independent of PPARgamma2 dysfunction. In subcutaneous white adipose tissue, L-PGDS KO mice exhibit a 4fold increase in UCP1 expression and a reduction in adipogenic marker aP2 expression. Phenotypes, overview
malfunction
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enzyme deficiency accelerates the growth of melanoma in mice. Enzyme deficiency results in functional changes of tumor endothelial cells such as accelerated vascular hyperpermeability, angiogenesis, and endothelial-to-mesenchymal transition in tumors, which in turn reduce tumor cell apoptosis
malfunction
the incidence of preterm birth is significantly reduced to 40% in enzyme-deficient knockout mice
malfunction
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double knockout mice, lacking lipocalin prostaglandin D synthase as well as PPARgamma2, have impaired carbohydrate and lipid metabolism with glucose tolerance compared to any other genotypes, their interscapular brown adipose tissue exhibits greater lipid content than that of wild-type mice, which is independent of PPARgamma2 dysfunction. In subcutaneous white adipose tissue, L-PGDS KO mice exhibit a 4fold increase in UCP1 expression and a reduction in adipogenic marker aP2 expression. Phenotypes, overview
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physiological function
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L-PGDS may fine-tune the all-trans retinoic acid signaling in melanocytes
physiological function
lipocalin type prostaglandin D synthase is a multi-functional protein acting as a somnogen (PGD2)-producing enzyme, an extracellular transporter of various lipophilic ligands, and an amyloid-beta chaperone in human cerebrospinal fluid
physiological function
lipocalin-type prostaglandin D synthase acts as both a PGD2 synthase and an extracellular transporter for small lipophilic molecules
physiological function
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H-PGDS plays a critical role in the development of allergic rhinitis, especially in the induction of late phase nasal obstruction
physiological function
lipocalin prostaglandin D synthase regulates synthesis of an important inflammatory and signaling mediator, prostaglandin D2
physiological function
lipocalin-type prostaglandin D synthase is a multi-functional protein, acting as a prostaglandin D2-producing enzyme and a lipid-transporter. It is involved in the biosynthesis of prostaglandin D2, acting as an endogenous somnogen and allergy response. Binding mechanism of small lipophilic molecules by the enzyme functioning as lipid transporter, e.g. of biliverdin, all-trans-retinoic acid, L-thyroxine (T4), progesterone, and genistein, thermodynamic parameters, overview. The enzme shows broad ligand selectivity for small lipophilic molecules, it binds heme metabolites with significantly higher affinity than other small lipophilic ligands
physiological function
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requirement of the enzyme for maintenance of subcutaneous white adipose tissue function. The enzyme and peroxisome proliferator-activated receptor gamma2 coordinate to regulate carbohydrate and lipid metabolism
physiological function
the enzyme shows a protective effect on H2O2-induced apoptosis in neuroblastoma cell line SH-SY5Y, the enzyme level is highly associated with H2O2-induced apoptosis. It protects against neuronal cell death by scavenging reactive oxygen species without losing its ligand-binding function. H2O2 reacts with the thiol of Cys65 of the enzyme
physiological function
higher enzyme concentrations significantly reduce the secretion of glucagon in alpha cells, which may contribute to the pathogenesis of diabetes
physiological function
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the enzyme has dual functional roles as a prostaglandin D2-synthesizing enzyme and as an extracellular transporter for diverse lipophilic compounds in the cerebrospinal fluid
physiological function
the enzyme plays a role in lipopolysaccharide-induced preterm birth
physiological function
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requirement of the enzyme for maintenance of subcutaneous white adipose tissue function. The enzyme and peroxisome proliferator-activated receptor gamma2 coordinate to regulate carbohydrate and lipid metabolism
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additional information
analysis of enzyme structure in complex with substrate analogue U44069, 9,11-epoxymethano-PGH2, and in ligand-free form. The catalytic Cys 65 thiol group occurs in two different conformations, each making a distinct hydrogen bond network to neighboring residues, mechanism of the cysteine nucleophile activation, and modelling of dynamics of protein-substrate and protein-product interactions, overview
additional information
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analysis of enzyme structure in complex with substrate analogue U44069, 9,11-epoxymethano-PGH2, and in ligand-free form. The catalytic Cys 65 thiol group occurs in two different conformations, each making a distinct hydrogen bond network to neighboring residues, mechanism of the cysteine nucleophile activation, and modelling of dynamics of protein-substrate and protein-product interactions, overview
additional information
binding of various lipophilic ligands in the hydrophobic cavity of lipocalin-type prostaglandin D synthase, i.e. hemin, biliverdin, and bilirubin, retinoids (all-trans and 9-cis retinoic acids), thyroids, steroids (progesterone, testosterone, and corticosterone), flavonoids (genistein, naringenin, and daidzein), the substrate PGH2 analogue U46619, and the fluorescence probe TNS, buffer-independent thermodynamic parameters, overview. The broad binding capability of the enzyme for ligands is realized by hydrophilic interactions delicately tuned by enthalpy-entropy compensation using combined effects of hydrophilic and hydrophobic interactions
additional information
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binding of various lipophilic ligands in the hydrophobic cavity of lipocalin-type prostaglandin D synthase, i.e. hemin, biliverdin, and bilirubin, retinoids (all-trans and 9-cis retinoic acids), thyroids, steroids (progesterone, testosterone, and corticosterone), flavonoids (genistein, naringenin, and daidzein), the substrate PGH2 analogue U46619, and the fluorescence probe TNS, buffer-independent thermodynamic parameters, overview. The broad binding capability of the enzyme for ligands is realized by hydrophilic interactions delicately tuned by enthalpy-entropy compensation using combined effects of hydrophilic and hydrophobic interactions
additional information
structure homology modelling using the solution structure of the C65A mouse L-PGDS, PDB code 2RQ0, as template, overview