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Query: UNIPROT:P06889 (Mol)
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In order to analyze the transcriptional regulation of the muscle-specific subunit of the human phosphoglycerate mutase (PGAM-M) gene, chimeric genes composed of the upstream region of the PGAM-M gene and the bacterial chloramphenicol acetyltransferase (CAT) gene were constructed and transfected into C2C12 skeletal myocytes, primary cultured cardiac muscle cells, and C3H10T1/2 fibroblasts. The expression of chimeric reporter genes was restricted in skeletal and cardiac muscle cells. In C2C12 myotubes and primary cultured cardiac muscle cells, the segment between nucleotides -165 and +41 relative to the transcription initiation site was sufficient to confer maximal CAT activity. This region contains two E boxes and one MEF-2 motif. Deletion and substitution mutation analysis showed that a single MEF-2 motif but not the E boxes had a substantial effect on skeletal and cardiac muscle-specific enhancer activity and that the cardiac muscle-specific negative regulatory region was located between nucleotides -505 and -165. When the PGAM-M gene constructs were cotransfected with MyoD into C3H10T1/2, the profile of CAT activity was similar to that observed in C2C12 myotubes. Gel mobility shift analysis revealed that when the nuclear extracts from skeletal and cardiac muscle cells were used, the PGAM-M MEF-2 site generated the specific band that was inhibited by unlabeled PGAM-M MEF-2 and muscle creatine kinase MEF-2 oligomers but not by a mutant PGAM-M MEF-2 oligomer. These observations define the PGAM-M enhancer as the only cardiac- and skeletal-muscle-specific enhancer characterized thus far that is mainly activated through MEF-2.
Mol Cell Biol 1992 Oct
PMID:A single MEF-2 site is a major positive regulatory element required for transcription of the muscle-specific subunit of the human phosphoglycerate mutase gene in skeletal and cardiac muscle cells. 132 54

In the rabbit and in the rat, which possess erythrocytes with high concentration of 2,3-bisphosphoglycerate, the 2,3-bisphosphoglycerate synthase activity increases more than two fold during reticulocyte maturation. Isolation of the enzymes with 2,3-bisphosphoglycerate synthase activity present in extracts of reticulocytes and mature erythrocytes by ion exchange fast liquid chromatography shows that the increase in the synthase activity is due to the accumulation of the bifunctional enzyme 2,3-bisphosphoglycerate synthase/phosphatase (EC2.7.5.4/EC3.1.3.13) which represents more than 80% of the synthase activity of the cell extracts. During reticulocyte maturation phosphoglycerate mutase (EC 5.4.2.1), which makes a small contribution to the 2,3-bisphosphoglycerate synthase activity in the erythroid cells, decreases in the rabbit and remains constant in the rat.
Mol Cell Biochem 1991 Apr 10
PMID:Increase of 2,3-bisphosphoglycerate synthase/phosphatase during maturation of reticulocytes with high 2,3-bisphosphoglycerate content. 165 83

In contrast to the species with erythrocytes of high 2,3-bisphosphoglycerate content, in the sheep the concentration of 2,3-bisphosphoglycerate decreases during maturation of reticulocytes. The decrease can be explained by the drop of the phosphofructokinase/pyruvate kinase and 2,3-bisphosphoglycerate synthase/2,3-bisphosphoglycerate phosphatase activity ratios that result from the decline of phosphofructokinase, pyruvate kinase, phosphoglycerate mutase and the bifunctional enzyme 2,3-bisphosphoglycerate synthase/phosphatase. The concentrations of fructose 2,6-bisphosphate and aldohexose 1,6-bisphosphates also decrease during sheep reticulocyte maturation in parallel to the 6-phosphofructo 2-kinase and the glucose 1,6-bisphosphate synthase activities.
Mol Cell Biochem 1990 Dec 03
PMID:2,3-Bisphosphoglycerate, fructose, 2,6-bisphosphate and glucose 1,6-bisphosphate during maturation of reticulocytes with low 2,3-bisphosphoglycerate content. 217 36

The numerical continuum electrostatic method presented previously (Warwicker, J. & Watson, H. C. (1982) J. Mol. Biol., 157, 671-679), is developed with an improved analysis of the protein-solvent system. Inclusion in the model of saturable solvent dielectric, and counterions is discussed and presented. A number of long-range electrostatic field calculations are made on bovine pancreatic trypsin inhibitor to demonstrate the differences between various solvent and counterion models. The long-range potential field, due to polar side-chain and alpha-helix dipole charge, is calculated for the glycolytic enzyme phosphoglycerate mutase. The positive potential in and around the catalytic cleft region is sufficiently large to suggest that it may play a role in long-range attraction of the enzyme's negatively charged substrates. Analogous systems with charge-charge interactions in solvent water are considered. It is suggested that a long-range enzyme-substrate attractive force-field may, in part, offset the repulsive energy arising from overlap of hydration shells between enzyme and substrate.
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PMID:Continuum dielectric modelling of the protein-solvent system, and calculation of the long-range electrostatic field of the enzyme phosphoglycerate mutase. 243 57

The phosphoglycerate mutase family is generally very well documented with respect to structure, evolution, and mode of action. However, a few individuals in the family remain relatively poorly characterized and will clearly require more detailed study. Furthermore, certain aspects of the detailed behavior of these enzymes are, as yet, incompletely understood and require further investigation. Cofactor-dependent monophosphoglycerate mutase and bisphosphoglycerate mutase are undoubtedly very closely related. Their amino acid sequences are strongly similar, they can form active heterodimers, and they catalyze the same three reactions, albeit at substantially different relative rates. Both enzymes catalyze a ping-pong type of reaction with a phosphohistidine intermediate. The presence of an additional phospho ligand at the active site of monophosphoglycerate mutase helps to explain why this enzyme is better at retaining the 2,3-bisphosphoglycerate intermediate and why it is thus more efficient (by a factor of about 10(3)) at catalyzing the interconversion of 3- and 2-phosphoglycerates. The reason why 1,3-bisphosphoglycerate is a better substrate for bisphosphoglycerate mutase than for monophosphoglycerate mutase (by a factor of about 30) is not yet apparent but presumably relates to the relative positioning of the two phospho-binding sites. Both enzymes are equally good as phosphatases when the reaction is activated by 2-phosphoglycollate. Available evidence indicates that these mutases are similar in many respects to the much smaller, cofactor-dependent monophosphoglycerate mutase from Schizosaccharomyces pombe, but further information is required to define the relationship more precisely. Cofactor-independent monophosphoglycerate mutase belongs to a quite distinct branch of the phosphoglycerate mutase family. It is not known at present whether this branch is related divergently or convergently to the cofactor-dependent monophosphoglycerate mutase/bisphosphoglycerate mutase branch. Existing evidence can be argued both ways. For example, the kinetic evidence shows a ping-pong type of reaction and would be consistent with a phosphohistidine intermediate as encountered in the other mutases. Thus the cofactor-independent enzyme may also have arisen by gene duplication--but, in this case, yielding an enzyme of about twice the size, with slightly different residues at the active site and C-terminal tail. An alternative possibility, of course, is that the two branches of the phosphoglycerate mutase family are quite unrelated in a divergent sense and are little more similar structurally than is, for example, the catalytically similar enzyme phosphoglucomutase.(ABSTRACT TRUNCATED AT 400 WORDS)
Adv Enzymol Relat Areas Mol Biol 1989
PMID:The phosphoglycerate mutases. 254 88

The PGM1 gene (also called GPM; Fraenkel 1982) coding for phosphoglyceromutase was isolated by functional complementation. When present on a multicopy vector and introduced into yeast cells it led to an about eightfold increase in specific enzymatic activity. This apparent overproduction was confirmed by SDS-polyacrylamide gel electrophoresis of crude extracts and at the transcriptional level by Northern analysis. By subcloning of the yeast DNA insertions of the plasmids originally isolated the PGM1 coding region was located within a 1.3 kb SalI-HindIII fragment. Integration at the chromosomal locus confirmed that the PGM1 gene had indeed been isolated. Southern analysis of genomic digests showed the same restriction patterns as the cloned sequences. However, a BamHI restriction polymorphism was observed. Furthermore, a repetitive element was found in the PGM1 flanking region. Finally, the chromosomal copy of the gene was deleted by replacement with a URA3 marker. The deletion mutants showed that the gene is not essential for yeast growing in the presence of a combination of glycerol and ethanol. However, growth was inhibited by glucose and neither glycerol nor ethanol alone were sufficient to support growth.
Mol Gen Genet 1987 Jan
PMID:Isolation of the yeast phosphoglyceromutase gene and construction of deletion mutants. 303 35

In the facultative halophyte Mesembryanthemum crystallinum (ice plant), salinity stress triggers significant changes in gene expression, including increased expression of mRNAs encoding enzymes involved with osmotic adaptation to water stress and the crassulacean acid metabolism (CAM) photosynthetic pathway. To investigate adaptive stress responses in the ice plant at the molecular level, we generated a subtracted cDNA library from stressed plants and identified mRNAs that increase in expression upon salt stress. One full-length cDNA clone was found to encode cofactor-independent phosphoglyceromutase (PGM), an enzyme involved in glycolysis and gluconeogenesis. Pgm1 expression increased in leaves of plants exposed to either saline or drought conditions, whereas levels of the mRNA remained unchanged in roots of hydroponically grown plants. Pgm1 mRNA was also induced in response to treatment with either abscisic acid or cytokinin. Transcription run-on experiments confirmed that Pgm1 mRNA accumulation in leaves was due primarily to increased transcription rates. Immunoblot analysis indicated that Pgm1 mRNA accumulation was accompanied by a modest but reproductible increase in the level of PGM protein. The isolation of a salinity-induced gene encoding a basic enzyme of glycolysis and gluconeogenesis indicates that adaptation to salt stress in the ice plant involves adjustments in fundamental pathways of carbon metabolism and that these adjustments are controlled at the level of gene expression. We propose that the leaf-specific expression of Pgm1 contributes to the maintenance of efficient carbon flux through glycolysis/gluconeogenesis in conjunction with the stress-induced shift to CAM photosynthesis.
Plant Mol Biol 1995 Oct
PMID:A salinity-induced gene from the halophyte M. crystallinum encodes a glycolytic enzyme, cofactor-independent phosphoglyceromutase. 757 74

We have previously demonstrated that maize (Zea mays) 2,3-bisphosphoglycerate-independent phosphoglycerate mutase (PGAM-i) is not related to 2,3-bisphosphoglycerate-dependent phosphoglycerate mutase. With the aid of specific anti-maize PGAM-i antibodies, we demonstrate here the presence of a closely related PGAM-i in other plants. We also describe the isolation and sequencing of a cDNA-encoding almond (Prunus amygdalus) PGAM-i that further demonstrates this relationship among plant PGAM-i. A search of the major databases for related sequences allowed us to identify some novel PGAM-i from different sources: plants (Arabidopsis thaliana, Oryza sativa and Antithamniom sp.), monera (Escherichia coli, Bacillus subtilis and Bacillus megaterium) and animals (Caenorhabditis elegans). All of these amino acid sequences share a high degree of homology with plant PGAM-i. These observations suggest that the PGAM-i from several biological kingdoms constitute a family of protein different from other proteins with related enzymatic function and arose from a common ancestral gene that has diverged throughout its evolution.
Comp Biochem Physiol B Biochem Mol Biol 1995 Oct
PMID:2,3-Bisphosphoglycerate-independent phosphoglycerate mutase is conserved among different phylogenic kingdoms. 758 58

Mcm1 is a multifunctional protein which plays a role both in the initiation of DNA replication and in the transcriptional regulation of diverse genes in Saccharomyces cerevisiae. The mcm1-1 mutation results in instability of minichromosomes and alpha-specific sterility. Second-site suppressors that restore minichromosome stability but not fertility to the mcm1-1 mutant were isolated. Two of the suppressors, pgm1-1 and pgm1-2, are mutant alleles of PGM1 which encodes a glycolytic enzyme, phosphoglycerate mutase. We show that the pgm1-1 mutation suppresses the minichromosome maintenance (Mcm) defect by increasing the protein activity or level of Mcm1-1 posttranscriptionally. This increase in the intracellular Mcm1-1 activity is sufficient to suppress the Mcm defect but only minimally suppresses the mating defect. Mutations in genes encoding other glycolytic enzymes, such as eno2::URA3, can also suppress the Mcm phenotype of mcm1-1. Suppression by these glycolytic enzyme mutations correlates with a reduced rate of glycolysis rather than a reduced rate of cell growth. This study suggests that in response to changes in their nutritional states yeast cells may attain homeostasis by modulating the activity of global regulators like Mcm1, which plays a central role in the regulation of energy-expensive anabolic processes.
Mol Cell Biol 1995 Aug
PMID:The yeast Mcm1 protein is regulated posttranscriptionally by the flux of glycolysis. 762 55

The GCR1 gene product is required for maximal transcription of yeast glycolytic genes and for growth of yeast strains in media containing glucose as a carbon source. Dominant mutations in two genes, SGC1 and SGC2, as well as recessive mutations in the SGC5 gene were identified as suppressors of the growth and transcriptional defects caused by a gcr1 null mutation. The wild-type and mutant alleles of SGC1 were cloned and sequenced. The predicted amino acid sequence of the SGC1 gene product includes a region with substantial similarity to the basic-helix-loop-helix domain of the Myc family of DNA-binding proteins. The SGC1-1 dominant mutant allele contained a substitution of glutamine for a highly conserved glutamic acid residue within the putative basic DNA binding domain. A second dominant mutant, SGC1-2, contained a valine-for-isoleucine substitution within the putative loop region. The SGC1-1 dominant mutant suppressed the GCR1 requirement for enolase, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, phosphoglycerate mutase, and pyruvate kinase gene expression. Expression of the yeast enolase genes was reduced three- to fivefold in strains carrying an sgc1 null mutation, demonstrating that SGC1 is required for maximal enolase gene expression. Expression of the enolase genes in strains carrying gcr1 and sgc1 double null mutations was substantially less than observed for strains carrying either null mutation alone, suggesting that GCR1 and SGC1 function on parallel pathways to activate yeast glycolytic gene expression.
Mol Cell Biol 1995 May
PMID:The GCR1 requirement for yeast glycolytic gene expression is suppressed by dominant mutations in the SGC1 gene, which encodes a novel basic-helix-loop-helix protein. 773 44


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