Phosphoglycerate Mutases Function as Reverse Regulated Isoenzymes in Synechococcus elongatus PCC 7942
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{"title"=>"Phosphoglycerate Mutases Function as Reverse Regulated Isoenzymes in Synechococcus elongatus PCC 7942", "type"=>"journal", "authors"=>[{"first_name"=>"Jiri", "last_name"=>"Jablonsky", "scopus_author_id"=>"56784139600"}, {"first_name"=>"Martin", "last_name"=>"Hagemann", "scopus_author_id"=>"7007133351"}, {"first_name"=>"Doreen", "last_name"=>"Schwarz", "scopus_author_id"=>"16677309500"}, {"first_name"=>"Olaf", "last_name"=>"Wolkenhauer", "scopus_author_id"=>"6603822253"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"368465895", "sgr"=>"84874601568", "pmid"=>"23484009", "scopus"=>"2-s2.0-84874601568", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "doi"=>"10.1371/journal.pone.0058281", "issn"=>"19326203"}, "id"=>"57f40434-d968-3327-9c23-82407e78bea2", "abstract"=>"Phosphoglycerate-mutase (PGM) is an ubiquitous glycolytic enzyme, which in eukaryotic cells can be found in different compartments. In prokaryotic cells, several PGMs are annotated/localized in one compartment. The identification and functional characterization of PGMs in prokaryotes is therefore important for better understanding of metabolic regulation. Here we introduce a method, based on a multi-level kinetic model of the primary carbon metabolism in cyanobacterium Synechococcus elongatus PCC 7942, that allows the identification of a specific function for a particular PGM. The strategy employs multiple parameter estimation runs in high CO2, combined with simulations testing a broad range of kinetic parameters against the changes in transcript levels of annotated PGMs. Simulations are evaluated for a match in metabolic level in low CO2, to reveal trends that can be linked to the function of a particular PGM. A one-isoenzyme scenario shows that PGM2 is a major regulator of glycolysis, while PGM1 and PGM4 make the system robust against environmental changes. Strikingly, combining two PGMs with reverse transcriptional regulation allows both features. A conclusion arising from our analysis is that a two-enzyme PGM system is required to regulate the flux between glycolysis and the Calvin-Benson cycle, while an additional PGM increases the robustness of the system.", "link"=>"http://www.mendeley.com/research/phosphoglycerate-mutases-function-reverse-regulated-isoenzymes-synechococcus-elongatus-pcc-7942", "reader_count"=>21, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>3, "Librarian"=>1, "Student > Doctoral Student"=>1, "Researcher"=>6, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>1, "Student > Master"=>2, "Student > Bachelor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>3, "Librarian"=>1, "Student > Doctoral Student"=>1, "Researcher"=>6, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>1, "Student > Master"=>2, "Student > Bachelor"=>2}, "reader_count_by_subject_area"=>{"Engineering"=>2, "Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>2, "Medicine and Dentistry"=>1, "Agricultural and Biological Sciences"=>9, "Physics and Astronomy"=>1, "Chemistry"=>2, "Computer Science"=>2}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>2}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Chemistry"=>{"Chemistry"=>2}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>9}, "Computer Science"=>{"Computer Science"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"United States"=>1}, "group_count"=>3}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/978483"], "description"=>"<p>For the purpose of comparison, the <u>dashed line</u> represents the single enzyme scenario from <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058281#pone-0058281-g003\" target=\"_blank\">Fig. 3</a>, 1.7-fold down-regulated PGM4 (merged solid lines from <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058281#pone-0058281-g003\" target=\"_blank\">Figure 3</a>). Further, two dual PGMs scenarios are presented. K<sub>eq</sub> and k<sub>M</sub> values for alpha PGM are from the best fit for single PGM scenario (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058281#pone-0058281-g004\" target=\"_blank\">Fig. 4</a>, open square) and V<sub>max</sub> for alpha PGM and all kinetic parameters for PGM beta were estimated to fit the experimental data in high CO<sub>2</sub> steady state. Alpha and beta stand for two PGMs in dual PGMs scenario. The <u>dotted line</u> shows the cooperation of co-regulated PGM4 and PGM1 (1.7- and 1.4-fold down-regulation, respectively). The <u>solid line</u> indicates the case in which reverse regulation of PGM2 and PGM4 takes a place (15.4-fold up-regulation and 1.7-fold down-regulation). The <u>blue line</u> indicates the scenario of three PGMs in which PGM1 (1.4-fold down-regulation) is considered as gamma PGM. The k<sub>M</sub> values for beta PGM are taken from the best fit of dual reverse PGMs scenario (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058281#pone-0058281-g004\" target=\"_blank\">Fig. 4</a>, open triangle). The <u>green line</u> indicates another triple PGMs scenario where k<sub>M</sub> values, both for beta and gamma PGMs, were varied. Note: each point represents an independent simulation run compared to experimental data - the lines improve the perception for the differences in match ratios and have no other meaning.</p>", "links"=>[], "tags"=>["transcriptional", "pgm", "isoenzyme", "genes"], "article_id"=>645444, "categories"=>["Biological Sciences", "Biochemistry", "Cell Biology", "Genetics", "Microbiology"], "users"=>["Jiri Jablonsky", "Martin Hagemann", "Doreen Schwarz", "Olaf Wolkenhauer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0058281.g005", "stats"=>{"downloads"=>1, "page_views"=>23, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Impact_of_reverse_and_similar_transcriptional_regulation_of_PGM_isoenzyme_genes_in_one_compartment_/645444", "title"=>"Impact of reverse and similar transcriptional regulation of PGM isoenzyme genes in one compartment.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-07 08:27:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/978488"], "description"=>"<p>ClustalW2 2.1 (<a href=\"http://www.ebi.ac.uk/Tools/\" target=\"_blank\">http://www.ebi.ac.uk/Tools/</a>) was employed as a tool for protein alignment analysis, codon table for bacteria was selected. PGMs 1–4 (<i>Synechococcus</i>) and two PSPs (<i>Hydrogenobacter thermophilus</i>) are highlighted. PGM3 is clustered with two PSPs.</p>", "links"=>[], "tags"=>["pgms", "psps"], "article_id"=>645448, "categories"=>["Biological Sciences", "Biochemistry", "Cell Biology", "Genetics", "Microbiology"], "users"=>["Jiri Jablonsky", "Martin Hagemann", "Doreen Schwarz", "Olaf Wolkenhauer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0058281.g006", "stats"=>{"downloads"=>1, "page_views"=>25, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Grouping_of_PGMs_and_PSPs_by_using_cluster_analysis_/645448", "title"=>"Grouping of PGMs and PSPs by using cluster analysis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-07 08:28:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/978490"], "description"=>"<div><p>Phosphoglycerate-mutase (PGM) is an ubiquitous glycolytic enzyme, which in eukaryotic cells can be found in different compartments. In prokaryotic cells, several PGMs are annotated/localized in one compartment. The identification and functional characterization of PGMs in prokaryotes is therefore important for better understanding of metabolic regulation. Here we introduce a method, based on a multi-level kinetic model of the primary carbon metabolism in cyanobacterium <i>Synechococcus elongatus</i> PCC 7942, that allows the identification of a specific function for a particular PGM. The strategy employs multiple parameter estimation runs in high CO<sub>2</sub>, combined with simulations testing a broad range of kinetic parameters against the changes in transcript levels of annotated PGMs. Simulations are evaluated for a match in metabolic level in low CO<sub>2</sub>, to reveal trends that can be linked to the function of a particular PGM. A one-isoenzyme scenario shows that PGM2 is a major regulator of glycolysis, while PGM1 and PGM4 make the system robust against environmental changes. Strikingly, combining two PGMs with reverse transcriptional regulation allows both features. A conclusion arising from our analysis is that a two-enzyme PGM system is required to regulate the flux between glycolysis and the Calvin-Benson cycle, while an additional PGM increases the robustness of the system.</p> </div>", "links"=>[], "tags"=>["phosphoglycerate", "mutases", "regulated", "isoenzymes", "pcc", "7942"], "article_id"=>645449, "categories"=>["Biological Sciences", "Biochemistry", "Cell Biology", "Genetics", "Microbiology"], "users"=>["Jiri Jablonsky", "Martin Hagemann", "Doreen Schwarz", "Olaf Wolkenhauer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0058281", "stats"=>{"downloads"=>3, "page_views"=>45, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Phosphoglycerate_Mutases_Function_as_Reverse_Regulated_Isoenzymes_in_Synechococcus_elongatus_PCC_7942__/645449", "title"=>"Phosphoglycerate Mutases Function as Reverse Regulated Isoenzymes in <em>Synechococcus elongatus</em> PCC 7942", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-03-07 08:29:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/1006338"], "description"=>"<p>Activity of PGMs is in the model described by reversible Michaelis-Menten kinetics. Note: V<sub>max</sub> values are normalized to the activity of RuBisCO. The routine employed for parameter estimation was a hybrid genetic algorithm.</p>", "links"=>[], "tags"=>["kinetic", "describing", "regulated", "dual", "pgms"], "article_id"=>666959, "categories"=>["Biological Sciences", "Biochemistry", "Cell Biology", "Genetics", "Microbiology"], "users"=>["Jiri Jablonsky", "Martin Hagemann", "Doreen Schwarz", "Olaf Wolkenhauer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0058281.t001", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Estimated_kinetic_parameters_for_the_best_fit_describing_the_reverse_regulated_dual_PGMs_scenario_/666959", "title"=>"Estimated kinetic parameters for the best fit describing the reverse regulated dual PGMs scenario.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-03-06 01:55:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/978467"], "description"=>"<p>The model includes the Calvin-Benson cycle, sucrose and glycogen synthesis, photorespiratory pathways, glycolysis and sink reactions, representing the adjacent pathways. Green color represents the reaction catalyzed by phosphoglycerate mutase (PGM) and indicates its cardinal position in the crossroads of metabolic pathways (need for complex model). Note: The reactions are described in the model by reversible and irreversible Michaelis-Menten kinetics; reversibility of particular reaction is indicated by two little arrows.</p>", "links"=>[], "tags"=>["carbon", "encoded", "kinetic", "pcc"], "article_id"=>645430, "categories"=>["Biological Sciences", "Biochemistry", "Cell Biology", "Genetics", "Microbiology"], "users"=>["Jiri Jablonsky", "Martin Hagemann", "Doreen Schwarz", "Olaf Wolkenhauer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0058281.g001", "stats"=>{"downloads"=>1, "page_views"=>22, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Scheme_of_the_primary_carbon_metabolism_encoded_as_a_kinetic_model_of_Synechococcus_elongatus_PCC_7942_/645430", "title"=>"Scheme of the primary carbon metabolism, encoded as a kinetic model of <i>Synechococcus elongatus</i> PCC 7942.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-07 08:23:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/978472"], "description"=>"<p>Note: synpcc7942_0485 probably represents a gene encoding a phosphoserine phosphatase but we cannot exclude if it functions as PGM.</p>", "links"=>[], "tags"=>["3pga", "annotated", "pgm", "isoenzymes", "cells", "pcc", "7942", "shifting"], "article_id"=>645433, "categories"=>["Biological Sciences", "Biochemistry", "Cell Biology", "Genetics", "Microbiology"], "users"=>["Jiri Jablonsky", "Martin Hagemann", "Doreen Schwarz", "Olaf Wolkenhauer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0058281.g002", "stats"=>{"downloads"=>1, "page_views"=>20, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparison_of_fold_changes_in_concentration_for_3PGA_and_in_expression_levels_of_the_four_annotated_PGM_isoenzymes_in_cells_of_Synechococcus_elongatus_PCC_7942_after_shifting_from_high_to_low_CO_2_level_/645433", "title"=>"Comparison of fold changes in concentration for 3PGA and in expression levels of the four annotated PGM isoenzymes in cells of <i>Synechococcus elongatus</i> PCC 7942 after shifting from high to low CO<sub>2</sub> level.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-07 08:25:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/978475"], "description"=>"<p>Figures represent the match between simulated and measured data in low CO<sub>2</sub> in dependence of estimated kinetic parameters (V<sub>max</sub> and k<sub>M</sub> values for preferred substrate and product) in high CO<sub>2</sub> for a single PGM scenario.The V<sub>max</sub>, fitted to steady state in high CO<sub>2</sub>, was modified by the amount of PGM isoforms taken from the changes in mRNA values (one by one) after shift from high to low CO<sub>2</sub>. Results are shown for randomly chosen set of twenty parameters estimation runs for PGM and the best fit (Nr. 12). The <b>left figure</b> shows the match for preferred product of PGM, 2-phosphoglycerate (2PGA). The <u>black solid line</u> shows the impact of 1.7-fold down-regulated enzyme, corresponding to PGM4; <u>gray contours</u> indicate the difference in matching the data if PGM is 15.4-fold up-regulated (corresponding to PGM2). In order to illustrate the impact of transcriptomic changes for the other two annotated PGMs, the results for 1.4-fold down-regulated (<u>circle</u>) and 2.7-fold up-regulated (<u>square</u>) isoenzymes are presented in the case of the best fit. The <b>right figure</b> shows the match for preferred substrate of PGM, 3-phosphoglycerate (3PGA); colors/lines have the same meaning as for the figure on the left. Notes: 1) the top boundary of axis y shows results equal or worse than match ratio equals to 3, 2) The match ratio is calculated as X/Y where X(Y) is a higher(lower) number from a pair of simulated and experimental values for a particular data point, 3) Fit from high CO<sub>2</sub> was included (saved as a result) if the difference between simulated and measured data was smaller than 15%, 4) each point represents an independent simulation run compared to experimental data - the lines improve the perception for the differences in match ratios and have no other meaning.</p>", "links"=>[], "tags"=>["simulated", "pgm", "dependence", "varying", "activities", "fitted", "transcript"], "article_id"=>645436, "categories"=>["Biological Sciences", "Biochemistry", "Cell Biology", "Genetics", "Microbiology"], "users"=>["Jiri Jablonsky", "Martin Hagemann", "Doreen Schwarz", "Olaf Wolkenhauer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0058281.g003", "stats"=>{"downloads"=>1, "page_views"=>22, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Quality_for_the_match_of_simulated_and_measured_data_in_low_CO_2_for_single_PGM_scenario_in_dependence_on_i_varying_PGM_activities_fitted_in_high_CO_2_and_ii_regulation_by_transcript_amounts_/645436", "title"=>"Quality for the match of simulated and measured data in low CO<sub>2</sub> for single PGM scenario in dependence on (i) varying PGM activities fitted in high CO<sub>2</sub> and (ii) regulation by transcript amounts.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-07 08:25:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/978478"], "description"=>"<p>The values k<sub>ms</sub> and k<sub>mp</sub> indicate the k<sub>M</sub> values for the preferred substrate and product (reversibility), respectively. Keq indicates the equilibrium constant. <b>Solid squares</b> denote independent runs of parameter estimation, presented in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058281#pone-0058281-g003\" target=\"_blank\">Fig. 3</a>, for single PGM scenario. <b>The open square</b> denotes the best fit for single PGM scenario. <b>Solid triangles</b> denote independent runs of parameter estimation, presented in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058281#pone-0058281-g005\" target=\"_blank\">Fig. 5</a>, for dual reverse regulated PGMs scenario for PGM beta. <b>The open triangle</b> denotes the best fit for dual reverse regulated PGMs scenario for PGM beta. <b>The open circle</b> denotes the best fit for triple PGMs scenario for PGM gamma. This analysis shows how multiple sets of kinetic parameters match experimental data in one steady state for unconstrainted parameter estimation.</p>", "links"=>[], "tags"=>["equilibrium", "constants", "pgm", "dual", "pgms"], "article_id"=>645439, "categories"=>["Biological Sciences", "Biochemistry", "Cell Biology", "Genetics", "Microbiology"], "users"=>["Jiri Jablonsky", "Martin Hagemann", "Doreen Schwarz", "Olaf Wolkenhauer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0058281.g004", "stats"=>{"downloads"=>1, "page_views"=>25, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Parameter_space_of_the_equilibrium_constant_and_ratio_of_k_M_constants_for_single_PGM_and_dual_PGMs_scenarios_/645439", "title"=>"Parameter space of the equilibrium constant and ratio of k<sub>M</sub> constants for single PGM and dual PGMs scenarios.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-07 08:26:11"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"2", "full-text"=>"2", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"2"}
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Relative Metric

{"start_date"=>"2013-01-01T00:00:00Z", "end_date"=>"2013-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Ecology and environmental sciences", "average_usage"=>[284, 475, 603, 722, 826, 928, 1026, 1129, 1225, 1310, 1390, 1468, 1549]}, {"subject_area"=>"/Ecology and environmental sciences/Environmental chemistry", "average_usage"=>[203, 348, 442, 542, 627, 713, 771, 830, 903, 967, 1053, 1107, 1155]}, {"subject_area"=>"/Physical sciences", "average_usage"=>[254, 431, 547, 651, 748, 842, 932, 1017, 1098, 1178, 1259, 1336, 1404]}]}
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