Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.5.1.18 (glutathione S-transferase)
22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The geographical distribution of the gene frequencies from loci: Hp, Tf, Gc, Pi, AcP1, GLO1, EsD, 6-PGD, PGM1 and RFLP's of the nuclear DNA of the loci HBG-2 (HindIII), HBB (AvaII), ApoB (XbaI), D7S8 (PstI), LDLR (HincII) and AT-3 was analysed in the Mongolian population. These data revealed the homogeneity of 18 local groups in Mongolia and extremely low genetic differences measured by GST. There was no differences in the average GST values between protein markers and nuclear DNA markers.
...
PMID:[Genetic differentiation of the Mongolian population. Comparative analysis of the geographic distribution of biochemical markers of genes and restriction fragment length polymorphism of nuclear DNA in the Mongolian population]. 136 22

The cellular localization of glutathione-requiring PGD synthetase, which catalyzes the predominant formation of PGD2 in various peripheral tissues, was investigated in adult rats by immunoperoxidase-staining with a polyclonal antibody specific for this enzyme. Although the 25 N-terminal amino acid residues of synthetase are 56% identical and 76% similar to those of several rat glutathione S-transferase subunits, the antibody cross-reacted only with synthetase in dot blotting and was nearly completely inactive with all transferase isozymes thus far purified. In Western blotting after SDS-PAGE of crude extracts of rat spleen, the antibody showed a single positive band at the same position as that of the purified enzyme (Mr = 26,000). The positive immunocytochemical stain was found in a number of histiocytes and/or dendritic cells in spleen, thymus, and Peyer's patch of intestine. The immunostain was also observed in such cells in lamina propria of the villus in small intestine and colon, in submucosal layer of stomach, and in Kupffer cells in liver. Immunoelectron microscopy confirmed that immunoreactivity of this enzyme was distributed in cytoplasm of those cells. Such immunoreactive cells were not observed in brain, spinal cord, kidney, heart, testis, and skeletal muscle. These observations suggest that PGD2 is produced by glutathione-requiring PGD synthetase localized in these types of APC in various tissues and may play a critical role in dictating the progression of immune responses.
...
PMID:The major source of endogenous prostaglandin D2 production is likely antigen-presenting cells. Localization of glutathione-requiring prostaglandin D synthetase in histiocytes, dendritic, and Kupffer cells in various rat tissues. 250 61

A total of 945 non-related individuals from four isolated population groups from the Northern Aegean Sea (Greece)--Alonissos, Oxilithos, Skopelos, and Glossa, has been typed for 16 polymorphic systems of the blood, namely A1A2B0, MNS., Rhesus (C, c, Cw, D, E, e), Kell, Duffy (a,b), Kidd (a); Hp, Tf subtypes, Gc, Gm (1, 2, 3, 5, 13), Km (1); aP, AK, PGM1, EsD, and 6-PGD. The distribution of phenotype and gene/haplotype frequencies shows a considerable interpopulational variability, which is discussed considering the history of these populations as well as the impact of locally acting microevolutionary factors such as drift and founder effects. The average coefficient of gene diversity GST comes to 0.0147, whereas Wahlund's variance is on average 0.0154, and Wright's Fst = 0.0147. Genetic distance analysis reveals a pattern of similarities, which is in conformity with the history of the populations under study.
...
PMID:Genetic studies in four populations of the northern Aegean Sea, Greece. 260 73

A survey was conducted to study the genetic differentiation among 16 tribal groups of Orissa, Madhya Pradesh, and Maharashtra belonging to different ethnic and linguistic affiliations. Sixteen hundred and fifteen blood samples from both sexes were tested for 5 red cell enzyme systems: ACP, ESD, PGD, GLO, LDH, and Hb pattern. Three hundred and nineteen male individuals were tested for G-6-PD enzyme deficiency. The distribution of the enzyme markers and Hb show a range of variation which are more or less within the Indian range. Cases of homozygous HbSS were detected in all the tribes except 3 tribes in Orissa. Two cases of LDH Cal-1 homozygote were found in two Dravidian language speaking Orissa tribes. The chi 2-values for testing the homogeneity of gene frequencies indicate a non-significant heterogeneity for all alleles in the individual system. Within population diversity seems to be larger than between population diversity. The degree of over all genetic differentiation as measured by GST value is 0.0154 +/- 0.0071.
...
PMID:Study of enzyme polymorphism and haemoglobin patterns amongst sixteen tribal populations of central India (Orissa, Madhya Pradesh, and Maharashtra). 826 Jul 22

Prostaglandin (PG) D2 is a major prostanoid produced in the central nervous system and mast cells, acting as a neuromodulator and an allergic and inflammatory mediator. PGD2 is readily dehydrated to produce PGs of the J series, such as PGJ2, delta 12-PGJ2, and 15-deoxy-delta 12, 14-PGJ2. We identified two distinct types of PGD synthase: one is glutathione independent, the lipocalin-type enzyme; and the other is glutathione-dependent, the hematopoietic enzyme. Lipocalin-type PGD synthase is localized in the central nervous system and genital organs, dominantly produced in the leptomeninges of the brain and pigmented epithelium of the retina, and is actively secreted as beta-trace into the cerebrospinal fluid and interphotoreceptor matrix, respectively. Since the enzyme binds all-trans- or 9-cis-retinoic acid with Kd of about 100 nM, it is considered to be a bifunctional protein acting as a PGD2-producing enzyme and an extracellular retinoid-transporter. Alternatively, we recently cloned the cDNA for hematopoietic PGD synthase, crystallized the recombinant enzyme, and determined the three-dimensional structure. The enzyme is the first member of the sigma class glutathione S-transferase (GST) from vertebrates and possesses a prominent cleft as the active site, which is never seen among other members of the GST family.
...
PMID:[New aspects on prostaglandin D synthases]. 950 6

A gene geographic analysis of the indigenous population of the Caucasian historical cultural province was carried out with a set of genetic markers extensively studied in the Adyges (39 alleles of 18 loci): AB0, ACP, C3, FY, GC, GLO, HP, KEL, LEW, MN, MNS, P, PGD, PGM1, RH-C, RH-D, RH-E, and TF. Genetic information on 160 Caucasian populations was used (on average, 65 populations per locus). A synthetic map of the first principal component clearly showed a division into two gene geographic provinces: Northern Caucasus and Transcaucasia. The component significantly differed across the Greater Caucasian Ridge. One of the major regions of extreme values corresponded to the Adyge region. A map of the second component revealed two poles, Northwestern (the Adyges) and Caspian, in gene pool variation of the Caucasian population. The analysis of the maps and the space of principal components showed that the Adyge population is an important component of the Caucasian gene pool. A map of genetic distance from all Caucasian populations to the Adyges showed that the north Caucasian populations (excluding the Ossetes) are the most genetically similar to the Adyges, while Georgians from the Kolkhida Valley and Azerbaijanians from the lowlands near the Caspian Sea and highland steppes are the most genetically remote from the Adyges. The genetic diversity (GST x 10(2)) of the entire Caucasian gene pool was studied. The average diversity of subpopulation within a Caucasian ethnos was GS-E = 0.81, the diversity of ethnoses within a linguistic family was GE-L = 0.83, and the diversity of linguistic families was GL-T = 0.58. The race classification of the Caucasian populations (GS-E = 0.81, GS-R = 0.80, GR-T = 0.76) proved to be more genetically informative than the linguistic one. The major parameters of the Adyges (total diversity HT = 0.364, heterozygosity HS = 0.361, and subpopulation diversity within the ethnos GS-E = 0.69) were similar to those averaged over the entire Caucasian population. A comparison with the same set of genetic markers showed that the interethnic diversity in the Caucasian region was lower than in the other north Eurasian regions (GS-E was 1.24 in the European region, 1.42 in the Ural region, 1.27 in Middle Asia, and 3.85 in Siberia).
...
PMID:[Genogeographic analysis of subdivided population. The Adyge gene pool in the Caucasian gene pool system]. 1050 70

Prostaglandin (PG) D synthase catalyzes the isomerization of PGH2, a common precursor of various prostanoids, to produce PGD2 in the presence of sulfhydryl compounds. PGD2 induces sleep, regulates nociception, inhibits platelet aggregation, acts as an allergic mediator, and is further converted to 9 alpha, 11 beta-PGF2 or the J series of prostanoids, such as PGJ2, delta 12-PGJ2, and 15-deoxy-delta 12,14-PGJ2. We have purified two distinct types of PGD synthase; one is the lipocalin-type enzyme and the other is the hematopoietic enzyme. We isolated the cDNA and the gene for each enzyme and determined the tissue distribution profile and the cellular localization in several animal species. Lipocalin-type PGD synthase is localized in the central nervous system and male genital organs of various mammals and the human heart and is secreted into cerebrospinal fluid, seminal plasma, and plasma, respectively. The human enzyme was identified as beta-trace, which is a major protein in human cerebrospinal fluid. This enzyme is considered to be a dual-function protein; it acts as a PGD2-producing enzyme and also as a lipophilic ligand-binding protein, because the enzyme binds retinoids, thyroids, and bile pigments, with high affinities. Hematopoietic PGD synthase is widely distributed in the peripheral tissues and localized in the antigen-presenting cells, mast cells, and megakaryocytes. The hematopoietic enzyme is the first recognized vertebrate homolog of the sigma class of glutathione S-transferase. X-ray crystallographic analyses and generation of gene-knockout and transgenic mice for each enzyme have been performed.
...
PMID:Prostaglandin D synthase: structure and function. 1066 96

Hematopoietic prostaglandin (PG) D synthase (PGDS) is the first identified vertebrate ortholog in the Sigma class of the glutathione S-transferase (GST) family and catalyzes both isomerization of PGH(2) to PGD(2) and conjugation of glutathione to 1-chloro-2, 4-dinitrobenzene. We introduced site-directed mutations of Tyr(8), Arg(14), Trp(104), Lys(112), Tyr(152), Cys(156), Lys(198), and Leu(199), which are presumed to participate in catalysis or PGH(2) substrate binding based on the crystallographic structure. Mutants were analyzed in terms of structure, GST and PGDS activities, and activation of the glutathione thiol group. Of all the mutants, only Y8F, W104I, K112E, and L199F showed minor but substantial differences in their far-UV circular dichroism spectra from the wild-type enzyme. Y8F, R14K/E, and W104I were completely inactive. C156L/Y selectively lost only PGDS activity. K112E reduced GST activity slightly and PGDS activity markedly, whereas K198E caused a selective decrease in PGDS activity and K(m) for glutathione and PGH(2) in the PGDS reaction. No significant changes were observed in the catalytic activities of Y152F and L199F, although their K(m) for glutathione was increased. Using 5,5'-dithiobis(2-nitrobenzoic acid) as an SH-selective agent, we found that only Y8F and R14E/K did not accelerate the reactivity of the glutathione thiol group under the low reactivity condition of pH 5.0. These results indicate that Lys(112), Cys(156), and Lys(198) are involved in the binding of PGH(2); Trp(104) is critical for structural integrity of the catalytic center for GST and PGDS activities; and Tyr(8) and Arg(14) are essential for activation of the thiol group of glutathione.
...
PMID:Structural basis of hematopoietic prostaglandin D synthase activity elucidated by site-directed mutagenesis. 1087 2

GSH-dependent prostaglandin D(2) synthase (PGDS) enzymes represent the only vertebrate members of class Sigma glutathione S-transferases (GSTs) identified to date. Complementary DNA clones encoding the orthologous human and rat GSH-dependent PGDS (hPGDS and rPGDS, respectively) have been expressed in Escherichia coli, and the recombinant proteins isolated by affinity chromatography. The purified enzymes were both shown to catalyse specifically the isomerization of prostaglandin (PG) H(2) to PGD(2). Each transferase also exhibited GSH-conjugating and GSH-peroxidase activities. The ability of hPGDS to catalyse the conjugation of aryl halides and isothiocyanates with GSH was found to be less than that of the rat enzyme. Whilst there is no difference between the enzymes with respect to their K(m) values for 1-chloro-2,4-dinitrobenzene, marked differences were found to exist with respect to their K(m) for GSH (8 mM versus 0.3 mM for hPGDS and rPGDS, respectively). Using molecular modelling techniques, amino acid substitutions have been identified in the N-terminal domain of these enzymes that lie outside the proposed GSH-binding site, which may explain these catalytic differences. The tissue-specific expression of PGDS also varies significantly between human and rat; amongst the tissues examined, variation in expression between the two species was most apparent in spleen and bone marrow. Differences in catalytic properties and tissue-specific expression of hPGDS and rPGDS appears to reflect distinct physiological roles for class Sigma GST between species. The evolution of divergent functions for the hPGDS and rPGDS is discussed in the context of the orthologous enzyme from chicken.
...
PMID:Mammalian class Sigma glutathione S-transferases: catalytic properties and tissue-specific expression of human and rat GSH-dependent prostaglandin D2 synthases. 1167 24

Prostaglandin (PG) D synthase (PGDS) catalyzes the isomerization of PGH(2) to PGD(2), which acts as an endogenous somnogen and an allergic mediator. There are two distinct types of PGDS: one is lipocalin-type PGDS (L-PGDS) localized in the central nervous system, male genitals, and heart; and the other is hematopoietic PGDS (H-PGDS) in mast cells and Th2 lymphocytes. L-PGDS is the same as beta-trace, a major protein in human cerebrospinal fluid, and is also secreted into the seminal plasma and plasma. The L-PGDS concentration in various body fluids is useful as a marker for various diseases such as renal failure and coronary atherosclerosis. H-PGDS is a cytosolic enzyme and is a member of the Sigma class of glutathione S-transferase. We determined the X-ray crystallographic structures of H-PGDS and L-PGDS. We also generated the gene-knockout (KO) mice and the human enzyme-overexpressing transgenic mice for each PGDS. L-PGDS-KO mice lacked PGE(2)-induced tactile allodynia and rebound of non-rapid eye movement sleep after sleep deprivation. Human L-PGDS-overexpressing transgenic mice showed an increase in non-rapid eye movement sleep due to accumulation of PGD(2) in the brain after tail clipping. H-PGDS-KO mice showed an allergic reaction weaker than that of the wild-type mice.
...
PMID:[Functional analyses of lipocalin-type and hematopoietic prostaglandin D synthases]. 1469 53


1 2 Next >>

---