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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Galactose transport and metabolism in Escherichia coli involves a multicomponent amphibolic pathway. Galactose transport is accomplished by two different galactose-specific transport systems. At least four of the genes and operons involved in galactose transport and metabolism have promoters containing similar regulatory sequences. These sequences are recognized by at least three regulators, Gal repressor (GalR), Gal isorepressor (GalS) and cAMP receptor protein (CRP), which modulate transcription from these promoters. The negative regulators, GalR and GalS, discriminate between utilization of the high-affinity (regulated by GalS) and low-affinity (regulated by GalR) transport systems, and modulate the expression of genes for galactose metabolism in an overlapping fashion. GalS is itself autogenously regulated and CRP dependent, while the gene for GalR is constitutive. The gal operon encoding the enzymes for galactose metabolism has two promoters regulated by CRP in opposite ways; one (P1) is stimulated and the other (P2) inhibited by CRP. Both promoters are strongly repressed by GalR but weakly by GalS. All but one of the constituent promoters of the gal regulon have two operators. The gal regulon has the potential to coordinate galactose metabolism and transport in a highly efficient manner, under a wide variety of conditions of galactose availability.
Mol Microbiol 1993 Oct
PMID:The galactose regulon of Escherichia coli. 793 15

The X-ray structure of the periplasmic glucose/galactose receptor (binding protein) of Salmonella typhimurium (GBP-S) has been refined at 1.7 A resolution with an R-factor of 19.0%. The model contains all 309 residues of the amino acid sequence, 153 water molecules, a calcium ion and beta-D-galactose. The protein consists of two very similar structural domains, each of which is composed a core of parallel beta-sheet flanked on both sides by alpha-helices. Three short stretches of amino acid chain (from symmetrically related portions of the structure) link the domains, and presumably act as a hinge to allow their relative movement in functionally important conformational changes. Galactose is bound between the domains, interacting with a number of side-chains from the loops lining the binding cleft. A combination of hydrogen bonding, hydrophobic and steric effects give rise to tight binding (dissociation constant 0.2 microM) and high specificity. Of nine hydrogen bonding groups, three are aspartate, three asparagine, one histidine (unprotonated), one arginine and one water, contributing 13 hydrogen bonds in total. Additional residues pack against (primarily) non-polar faces of the sugar molecule. The precise arrangement of the hydrogen bonding and hydrophobic residues results in an enclosed binding site with a shape that is a composite of those of the allowed sugar molecules. It is presumed that ligands bind to a more open form of the receptor that then closes by rotation in the hinge. Comparison with the GBP-S structure solved earlier in complex with glucose shows no significant changes, even for the aspartate residue most directly involved with the different sugars. Comparison with the galactose/glucose receptor of Escherichia coli indicates that these two proteins are very similar in overall structure, with the main difference being a 2 to 3 degrees rotation in the hinge. This difference appears to be the result of different crystal packing for the two proteins; it is likely that both conformations are normally found in solution.
J Mol Biol 1993 Oct 20
PMID:The 1.7 A refined X-ray structure of the periplasmic glucose/galactose receptor from Salmonella typhimurium. 824 May 51

Glucose added to the medium was found to enhance superoxide production by isolated circulating neutrophils from both diabetic and normal subjects, but quantitatively the enhancement decreased from 4 to 50 mmole/liter. Galactose up to 50 mmole/liter had no effect on superoxide production in cells from the control subjects, but appeared to depress it in those from diabetics. No correlations were found between indices of the degree of hyperglycemia (plasma glucose and hemoglobin A1c) and the magnitude of the respiratory burst in cells from diabetics. When the isolated cells from normal and diabetic subjects were restored to a medium containing glucose at the original concentration in plasma at phlebotomy, the rate of superoxide production was approximately doubled in every case and there was no significant difference between diabetic and normal cells. Preincubation of cells for 1 hr in the presence of 0-50 mmole/liter glucose or galactose prior to activation had no significantly depressant effect on the respiratory burst except at 50 mmole/liter glucose in diabetic cells. It is concluded that circulating neutrophils from the diabetic population under the conditions studied are just as competent as control cells in their ability to sustain superoxide production over a wide range of energy availability.
Exp Mol Pathol 1993 Jun
PMID:Superoxide production by neutrophils from diabetics and normal subjects in response to glucose and galactose. 839 Sep 41

Galactose metabolism in all organisms is catalyzed by three enzymatic steps: the galactokinase, galactose-1-phosphate uridyltransferase, and UDP galactose 4'-epimerase reactions. We report here the molecular cloning, characterization, and mapping of a full-length cDNA encoding human UDP-galactose 4'-epimerase (GALE). Our cDNA is 1488 bp long and matches the mRNA size of 1.5 kg detected in fibroblasts and lymphoblasts. The human GALE cDNA encodes a predicted protein of 348 amino acids with a molecular mass of 38,266. The human GALE enzyme is 87% identical to the rat protein, 53% identical to the homologous GAL10 protein from the yeast Kluyveromyces lactis, and 51% identical to the galE protein from the prokaryote Escherichia coli. This extraordinary degree of sequence identity has allowed us to build a homology model of the human protein based on the bacterial crystal structure. This predicted human structure is very similar to the E. coli galE enzyme, suggesting that both enzymes use similar mechanisms. The human gene encoding GALE maps, as expected, to a single locus on chromosome 1 and appears to be compact. The human GALE gene is structurally intact in 19 patients with epimerase-deficiency galactosemia, an inborn error of metabolism secondary to GALE deficiency. Therefore, we propose that this disorder is due to small mutations within the gene.
Biochem Mol Med 1995 Oct
PMID:Molecular cloning, characterization, and mapping of a full-length cDNA encoding human UDP-galactose 4'-epimerase. 859 31

A series of yeast expression plasmids which comprise segments of the cDNA sequences encoding rat topo II alpha have been constructed. The transcription of these constructs is under the control of the yeast GAL1 promoter. Galactose-dependent expression of the cloned rat topo II alpha cDNA complemented a yeast top2ts mutation, as well as a deletion mutation at the yeast TOP2 locus. Truncation of 12 N-terminal amino acids and/or 158 C-terminal amino acids of rat topo II alpha had no effect on its ability functionally to substitute for top2ts. Moreover, a cDNA construct with mutated putative leucine zipper domain (amino acids 993-1013) retained the complementation activity. These observations suggest that transformants capable of conditional topo II alpha expression can be exploited as a useful model system for studies on the structure-function relationships of wild-type and mutated topo II alpha, as well as the interplay of potential antitumor drugs with the enzyme.
Mol Gen Genet 1996 Nov 27
PMID:Complementation of a yeast top2ts mutation by a cDNA encoding rat DNA topoisomerase II alpha. 900 90

Extracts of human liver were found to contain activities which copurified and coeluted with the two major subtypes of mediators (type A and type P) isolated from insulin-stimulated rat liver. The putative type A mediator from human liver inhibited cAMP-dependent protein kinase from bovine heart, decreased phosphoenolypyruvate carboxykinase mRNA levels in rat hepatoma cells, and stimulated lipogenesis in rat adipocytes. The putative type P mediator stimulated bovine heart pyruvate dehydrogenase phosphatase. Both fractions were able to stimulate proliferation of EGFR T17 fibroblasts and the type A was able to support growth in organotypic cultures of chicken embryo cochleovestibular ganglia. Both activities were resistant to Pronase treatment and the presence of carbohydrates, phosphate, and free-amino groups were confirmed in the two fractions. These properties are consistent with the structure/ function characteristics of the type A and P inositolphosphoglycans (IPG) previously characterized from rat liver. Further, the ability of the human-derived mediators to interact with rat adipocytes and bovine-derived metabolic enzymes suggests similarity in structure between the mediators purified from different species. Galactose oxidase-susceptible membrane-associated glycosylphosphatidylinositols (GPI) have been proposed to be the precursors of IPG. GPI was purified from human liver membranes followed by treatment with galactose oxidase and reduction with NaB3H4. Serial t.l.c. revealed three radiolabeled bands which comigrated with the putative GPI precursors found in rat liver. These galactose-oxidase-reactive lipidic compounds, however, were only partially susceptible to hydrolysis with phosphatidylinositol-specific phospholipase C from Bacillus thuringiensis and were resistant to glycosylphosphatidylinositol-specific phospholipase C from Trypanosoma brucei. These data indicate that IPG molecules with insulin-like biological activities are present in human liver.
Biochem Mol Med 1997 Aug
PMID:Isolation and partial characterisation of insulin-mimetic inositol phosphoglycans from human liver. 925 87

Classical galactosemia, characterized clinically by acute hepatic dysfunction, sepsis, cataract, and failure to thrive, is caused by deficiency of galactose-1-phosphate uridyltransferase (GALT). Galactose restriction normalizes these acute symptoms; however, long-term complications such as intellectual deficits and ovarian failure are conspicuous in the majority of patients. Here we report two Turkish siblings with classical galactosemia. The clinical course of the two children differed markedly: only the older girl suffered from severe acute symptoms during the neonatal period, and she developed greater mental retardation than her younger affected brother. The functional activity of GALT was virtually absent in each affected children. The mother and two healthy siblings exhibited approximately 50% normal GALT activity and the father approximately 25%. Molecular analysis revealed that these two galactosemic siblings were homozygous for a stop codon mutation of E340X in GALT exon 10. Moreover, two additional mutations, a neutral polymorphism L218L and N314D, which are typical for the Duarte-I variant, were found in the same GALT allele. The two healthy siblings and the parents were heterozygous for these combinations of mutations. In addition, the father's second GALT allele revealed three intron mutations at nucleotide position 1105 (G-->C), 1323 (G-->A) and 1391 (G-->A) and the N314D mutation, which correspond to the mutations of Duarte-2 variant. Our findings indicate that in classical galactosemia several distinct mutations can be present in one allele (in cis) of the GALT gene. Therefore it seems to be necessary to examine all introns and exons of the GALT gene in galactosemic patients who do not carry the Q188R mutation or another frequent mutation in the GALT gene.
J Mol Med (Berl) 1998 Sep
PMID:Simultaneous occurrence of various mutations and polymorphisms in cis and in trans of the galactose-1-phosphate uridyltransferase gene in a Turkish family with classical galactosemia. 976 50

Species- and genus-specific antigenic determinants of total serological activity of plague agent lipopolysaccharide (LPS) were detected for the first time with a panel of monoclonal antibodies (MAb) in Y. pestis core polysaccharide in the R-form. MAb specifically bind radicals on one or several monosaccharides of core LPS. Galactose, fucose, and mannose contain common antigenic determinants for enterobacteria; glucosamine, glucose, ribose, xylose, and 2-ketodeoxyoctanoic acid (KDO) contain determinants for Y. pestis and Y. pseudotuberculosis; and epitopes differentiating the two latter agents by the carbohydrate component are localized on glucosamine, mannose, xylose, and KDO. Epitopes common for the Enterobacteriaceae family and species-specific epitopes, two of which are identic to core polysaccharide radicals, are situated on Y. pestis lipid A.
Mol Gen Mikrobiol Virusol 1998
PMID:[Study of antigenic determinants of Yersinia pestis lipopolysaccharide using monoclonal antibodies]. 981 23

Glucose produces multiple effects in Saccharomyces cerevisiae, as it controls the expression of many genes and the activity of various enzymes. However, the elements involved in glucose signaling are not well characterized. In this work the capacity of galactose to bring about the same effects than glucose has been assessed. Galactose mimics glucose only partially; it is suggested that it does not interact with a "sensor" in the plasma membrane and that it produces a weaker intracellular signal than glucose. To examine whether trehalose-6P synthase (Tps1) is required to transduce the glucose signal, we have constructed a tps1 hxk2/tps1 HXK2 strain which, at difference of a tps1 strain, grows on glucose, and, at difference of a tps1 hxk2 strain, still possess the Hxk2 protein, possibly involved in glucose repression. From the response of this strain to glucose, we conclude that Tps1 does not play a prominent role in glucose signaling.
Mol Cell Biol Res Commun 1999 Apr
PMID:Glucose signaling in yeast is partially mimicked by galactose and does not require the Tps1 protein. 1032 78

Encystation of Entamoeba invadens parasites is prevented by the presence of free galactose or N-acetylglucosamine in the encystation medium. Galactose prevents the formation of amoeba cellular aggregates which develop during the early phase of encystation, suggesting the presence of functional cell surface galactose-binding molecules, whereas N-acetylglucosamine allows aggregation to occur and prevents cyst formation at a later point. While studying sugar inhibition of amoeba encystation, it was found that high efficiency encystation required the inclusion in encystation medium of precise amounts of polyvalent galactose-terminated molecules, and these molecules could be supplied by serum or by defined glycoconjugates, including mucin. Addition of free galactose to encystation medium prevented the accumulation of three transcripts which are normally upregulated during encystation, and N-acetylglucosamine prevented accumulation of one of the transcripts. These results suggest the presence of distinct sugar-sensitive pathways that regulate differentiation of the amoeba trophozoite into infectious cysts.
Mol Biochem Parasitol 1999 Jul 30
PMID:Regulation of Entamoeba invadens encystation and gene expression with galactose and N-acetylglucosamine. 1047 77


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