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Query: UNIPROT:P06889 (Mol)
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Bacillus stearothermophilus phosphatase PhoE is a member of the cofactor-dependent phosphoglycerate mutase superfamily possessing broad specificity phosphatase activity. Its previous structural determination in complex with glycerol revealed probable bases for its efficient hydrolysis of both large, hydrophobic, and smaller, hydrophilic substrates. Here we report two further structures of PhoE complexes, to higher resolution of diffraction, which yield a better and thorough understanding of its catalytic mechanism. The environment of the phosphate ion in the catalytic site of the first complex strongly suggests an acid-base catalytic function for Glu83. It also reveals how the C-terminal tail ordering is linked to enzyme activation on phosphate binding by a different mechanism to that seen in Escherichia coli phosphoglycerate mutase. The second complex structure with an unusual doubly covalently bound trivanadate shows how covalent modification of the phosphorylable His10 is accompanied by small structural changes, presumably to catalytic advantage. When compared with structures of related proteins in the cofactor-dependent phosphoglycerate mutase superfamily, an additional phosphate ligand, Gln22, is observed in PhoE. Functional constraints lead to the corresponding residue being conserved as Gly in fructose-2,6-bisphosphatases and Thr/Ser/Cys in phosphoglycerate mutases. A number of sequence annotation errors in databases are highlighted by this analysis. B. stearothermophilus PhoE is evolutionarily related to a group of enzymes primarily present in Gram-positive bacilli. Even within this group substrate specificity is clearly variable highlighting the difficulties of computational functional annotation in the cofactor-dependent phosphoglycerate mutase superfamily.
J Mol Biol 2003 Jan 17
PMID:Structures of phosphate and trivanadate complexes of Bacillus stearothermophilus phosphatase PhoE: structural and functional analysis in the cofactor-dependent phosphoglycerate mutase superfamily. 1249 92

Several microbial pathogens augment their invasive potential by binding and activating human plasminogen to generate the proteolytic enzyme plasmin. Yeast cells and cell wall proteins (CWP) of the human pathogenic fungus Candida albicans bound plasminogen with a K(d) of 70 +/- 11 nM and 112 +/- 20 nM respectively. Bound plasminogen could be activated to plasmin by mammalian plasminogen activators; no C. albicans plasminogen activator was detected. Binding of plasminogen to CWP and whole cells was inhibited by epsilon ACA, indicating that binding was predominantly to lysine residues. Candida albicans mutant strains defective in protein glycosylation did not show altered plasminogen binding, suggesting that binding was not mediated via a surface lectin. Binding was sensitive to digestion by basic carboxypeptidase, implicating C-terminal lysine residues in binding. Proteomic analysis identified eight major plasminogen-binding proteins in isolated CWP. Five of these (phosphoglycerate mutase, alcohol dehydrogenase, thioredoxin peroxidase, catalase, transcription elongation factor) had C-terminal lysine residues and three (glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase and fructose bisphosphate aldolase) did not. Activation of plasminogen could potentially increase the capacity of this pathogenic fungus for tissue invasion and necrosis. Although surface-bound plasmin(ogen) degraded fibrin, no direct evidence for a role in invasion of endothelial matrix or in penetration and damage of endothelial cells was found.
Mol Microbiol 2003 Mar
PMID:Candida albicans binds human plasminogen: identification of eight plasminogen-binding proteins. 1262 18

The roots of alternate-bearing citrus (Murcott, a Citrus reticulata hybrid) trees undergo extreme fluctuations of carbohydrate abundance and starvation. Using this system, we investigated the effect of root carbohydrate (total soluble sugar, sucrose and starch) depletion on carbohydrate-related gene expression. A series of genes, including those coding for starch phosphorylase ( STPH-L and STPH-H), ADP-glucose pyrophosphorylase, small subunit ( Agps), R1, plastidic ADP/ATP transporter ( AATP), phosphoglucomutase ( PGM-P and PGM-C), sucrose synthase ( CitSuS1 and CitSuSA), sucrose transporter ( SUT1 and SUT2), hexokinase ( HK) and alpha-amylase ( alpha-AMY), have been isolated and their expression analyzed. The genes were found to respond differentially to carbohydrate depletion. STPH-L, STPH-H, Agps, R1, AATP, PGM-P, PGM-C, CitSuS1 and HK were down-regulated while SUT1 and alpha-AMY were up-regulated during carbohydrate depletion. Two other genes, CitSuSA and SUT2, did not respond to carbohydrate depletion. Fruit removal, which interrupted the carbohydrate depletion induced by heavy fruiting, reversed these gene expression patterns. Trunk girdling and whole-plant darkening treatments, which brought about root carbohydrate depletion, induced the same changes in gene expression obtained in the alternate-bearing system. The possible roles of the up- and down-regulated genes in the metabolism of carbohydrate-depleted citrus roots are discussed. Although the specific signals involved have not been determined, the results support the feast/famine hypothesis of carbohydrate regulation proposed by Koch [K.E. Koch (1996) Annu Rev Plant Physiol Plant Mol Biol 47:509-540].
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PMID:Effects of carbohydrate starvation on gene expression in citrus root. 1272 44

Phosphoglycerate mutases catalyze the isomerization of 2 and 3-phosphoglycerates, and are essential for glucose metabolism in most organisms. Here, we further characterize the 2,3-bisphosphoglycerate-independent phosphoglycerate mutase (iPGM) from Bacillus stearothermophilus by determination of a high-resolution (1.4A) crystal structure of the wild-type enzyme and the crystal structure of its S62A mutant. The mutant structure surprisingly showed the replacement of one of the two catalytically essential manganese ions with a water molecule, offering an additional possible explanation for its lack of catalytic activity. Crystal structures invariably show substrate phosphoglycerate to be entirely buried in a deep cleft between the two iPGM domains. Flexibility analyses were therefore employed to reveal the likely route of substrate access to the catalytic site through an aperture created in the enzyme's surface during certain stages of the catalytic process. Several conserved residues lining this aperture may contribute to orientation of the substrate as it enters. Factors responsible for the retention of glycerate within the phosphoenzyme structure in the proposed mechanism are identified by molecular modeling of the glycerate complex of the phosphoenzyme. Taken together, these results allow for a better understanding of the mechanism of action of iPGMs. Many of the results are relevant to a series of evolutionarily related enzymes. These studies will facilitate the development of iPGM inhibitors which, due to the demonstrated importance of this enzyme in many bacteria, would be of great potential clinical significance.
J Mol Biol 2003 May 09
PMID:Insights into the catalytic mechanism of cofactor-independent phosphoglycerate mutase from X-ray crystallography, simulated dynamics and molecular modeling. 1272 63

In this study six simple sequence repeats (SSR or microsatellites) were selected for their ability to fingerprint a total of 60 commercial clones of Populus deltoides Marsh. and Populus x canadensis Moench (typically derived from crosses between Populus nigra L and P. deltoides) and to characterize a natural population of P. nigra growing along the Ticino river in the North of Italy. Out of six SSRs used, four microsatellite loci were found to have alleles which were species-specific to P. deltoides and could therefore be used as markers for introgression of P. deltoides into P. nigra. In the studied region hybrid poplars and P. deltoides commercial clones are cultivated as monoclonal stands close to the area where black poplar has its natural habitat. SSR analysis was performed to investigate whether there was evidence of introgression between the natural population and the monoclonal plantations of hybrids and P. deltoides clones cultivated in the surrounding area. Three stages of the natural population were analysed: a group of old trees about a hundred years old, a younger population (aged 2-30 years) and the seedlings of three females of this population. Alleles specific to P. deltoides were detected only in the old cohort of the natural population, while no introgression was observed in the younger individuals and their progenies. These results were also confirmed by isozyme analysis of loci PGI-B, PGM and LAP-A, which were previously identified as diagnostic for P. nigra, P. deltoides and P.xcanadensis.
Mol Ecol 2003 Aug
PMID:Molecular analysis of natural populations of Populus nigra L intermingled with cultivated hybrids. 1285 27

We previously isolated a partial soybean cDNA clone whose transcript abundance is increased upon infection by the sedentary, endoparasitic soybean cyst nematode Heterodera glycines. We now isolated the corresponding full-length cDNA and determined that the predicted gene product was similar to the group of cofactor-dependent phosphoglycerate mutase/bisphosphoglycerate mutase enzymes (PGM/bPGM; EC 5.4.2.1/5.4.2.4). We designated the corresponding soybean gene GmPGM. PGM and bPGM are key catalysts of glycolysis that have been well characterized in animals but not plants. Using the GmPGM cDNA sequence, we identified a homologous Arabidopsis thaliana gene, which we designated AtPGM. Histochemical GUS analyses of transgenic Arabidopsis plants containing the AtPGM promoter ::GUS construct revealed that the AtPGM promoter directs GUS expression in uninfected plants only to the shoot and root apical meristems. In infected plants, GUS staining also is evident in the nematode feeding structures induced by the cyst nematode Heterodera schachtii and by the root-knot nematode Meloidogyne incognita. Furthermore, we discovered that the AtPGM promoter was down-regulated by abscisic acid and hydroxyurea, whereas it was induced by sucrose, oryzalin, and auxin, thereby revealing expression characteristics typical of genes with roles in meristematic cells. Assessment of the auxin-inducible AUX1 gene promoter (a gene coding for a polar auxin transport protein) similarly revealed feeding cell and meristem expression, suggesting that auxin may be responsible for the observed tissue specificity of the AtPGM promoter. These results provide first insight into the possible roles of PGM/bPGM in plant physiology and in plant-pathogen interactions.
Plant Mol Biol 2003 Nov
PMID:Expression of an Arabidopsis phosphoglycerate mutase homologue is localized to apical meristems, regulated by hormones, and induced by sedentary plant-parasitic nematodes. 1501 Jun 16

We considered the contribution of two mitochondrial and two nuclear data sets for the phylogenetic reconstruction of 22 species of seed beetles in the genus Curculio (Coleoptera: Cuculionidae). A phylogenetic tree from representatives found on various hosts was inferred from a combined data set of mitochondrial DNA cytochrome oxidase subunit I, mitochondrial cytochrome b, nuclear elongation factor 1alpha, and nuclear phosphoglycerate mutase, used for the first time as a molecular marker. Separate parsimony analyses of each data set showed that individual gene trees were mainly congruent and often complementary in the support of clades but the analysis was complicated by failure of PCR amplification of nuclear genes for many taxa and hence missing data entries. When the four gene partitions were combined in a simultaneous analysis despite the missing data, this increased the resolution and taxonomic coverage compared to the individual source trees. Alternative approaches of combining the information via supertree methodology produced a comparatively less resolved tree, and hence seem inferior to combining data matrices even in cases where numerous taxa are missing. The molecular data suggest a classification of the European species into two species groups that are in accordance with morphological characteristics but the data do no support any of the previously recognised American species groups.
Mol Phylogenet Evol 2004 Aug
PMID:The phylogeny of acorn weevils (genus Curculio) from mitochondrial and nuclear DNA sequences: the problem of incomplete data. 1522 41

Eukaryotic cilia and flagella are long, thin organelles, and diffusion from the cytoplasm may not be able to support the high ATP concentrations needed for dynein motor activity. We discovered enzyme activities in the Chlamydomonas reinhardtii flagellum that catalyze three steps of the lower half of glycolysis (phosphoglycerate mutase, enolase, and pyruvate kinase). These enzymes can generate one ATP molecule for every substrate molecule consumed. Flagellar fractionation shows that enolase is at least partially associated with the axoneme, whereas phosphoglycerate mutase and pyruvate kinase primarily reside in the detergent-soluble (membrane + matrix) compartments. We further show that axonemal enolase is a subunit of the CPC1 central pair complex and that reduced flagellar enolase levels in the cpc1 mutant correlate with the reduced flagellar ATP concentrations and reduced in vivo beat frequencies reported previously in the cpc1 strain. We conclude that in situ ATP synthesis throughout the flagellar compartment is essential for normal flagellar motility.
Mol Biol Cell 2005 Oct
PMID:ATP production in Chlamydomonas reinhardtii flagella by glycolytic enzymes. 1603 Feb 51

Aims/background-In humans there are three phosphoglycerate mutase (PGM, EC 5.4.12.1) isoenzymes (MM, MB and BB) which have similar distribution and developmental pathways to creatine kinase (CK, EC 2.7.3.2) isoenzymes. Total serum PGM activity increases in acute myocardial infarction with the same time course as creatine kinase activity. The present study was undertaken to determine changes in the activity of PGM and its isoenzymes after acute myocardial infarction.Methods-PGM activity was measured spectrophotometrically, by coupling the formation of 2-phosphoglycerate from 3-phosphoglycerate with enolase, pyruvate kinase and lactate dehydrogenase catalysed reactions. Inter- and intra-assay reproducibility was assessed. PGM isoenzyme activities were measured using cellulose acetate electrophoresis.Results-Total PGM activity in serum was increased in patients with a confirmed diagnosis of acute myocardial infarction. PGM activity peaked 12 to 24 hours after the onset of symptoms and returned to normal values within 48 hours. Electrophoretic analysis of serum from healthy subjects showed a band corresponding to BB-PGM and two other artefactual bands that did not correspond to adenylate kinase. After myocardial infarction, BB-PGM activity increased and MB-PGM and MM-PGM could be detected. On immunoblot analysis, normal serum contained an inactive form of MM-PGM with a smaller molecular weight than that of PGM tissue isoenzymes.Conclusions-Total serum PGM activity increased in patients with acute myocardial infarction, following the same temporal course as creatine kinase activity. The increase in MM-PGM and MB-PGM activities in these patients was not as high as expected. It is suggested that PGM isoenzymes, after release into the blood, undergo postsynthetic, probably proteolytic, transformation.
Clin Mol Pathol 1996 Oct
PMID:Activity of phosphoglycerate mutase and its isoenzymes in serum after acute myocardial infarction. 1669 92

Coexisting bisexual and unisexual populations of individuals belonging to the genus Heterocypris are found in ephemeral freshwater ponds on the island of Lampedusa (Pelagie Islands, Italy). Different reproductive modes were associated with a peculiar morphological trait: a lamella hyalina on the posterior margin of the left valve was observed in amphimictic females, a feature missing in apomictic females. In order to clarify the phylogenetic relationships among taxa with different morphological traits and reproductive modes, we used four polymorphic enzyme loci (GPI, ICD2, MPI and PGM) and mitochondrial DNA 16S ribosomal sequences. We identified three main evolutionary units that showed a combination of morphological and reproductive characteristics: (1) amphimictic females of H. barbara with a lamella hyalina, according to the typical feature of the species, and apomictic females of H. barbara without lamella that are sympatric in one temporary pond; (2) apomictic females of H. incongruens without a lamella, as typical of the species; (3) apomictic females without a lamella, living in sympatry with H. barbara, but characterised by a high genetic diversity from both H. incongruens and H. barbara. We discuss the possible origin of apomictic lineages as a result of independent transition episodes to apomixis from different sexual ancestors. Time of divergence reflected the genetic differentiation within and among multiple ancestors and different possible routes to parthenogenesis.
Mol Phylogenet Evol 2007 Sep
PMID:Phylogenetic relationships of coexisting Heterocypris (Crustacea, Ostracoda) lineages with different reproductive modes from Lampedusa Island (Italy). 1755 7


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