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Escherichia coli K-12 substr. MG1655 Enzyme: glucose-1-phosphate adenylyltransferase



Gene: glgC Accession Numbers: EG10379 (EcoCyc), b3430, ECK3416

Regulation Summary Diagram: ?

Subunit composition of glucose-1-phosphate adenylyltransferase = [GlgC]4

Summary:
Glucose-1-phosphate adenylyltransferase catalyzes the rate-limiting first step in the biosynthesis of glycogen. The enzyme is allosterically activated by the glycolytic intermediate fructose-1,6-bisphosphate and inhibited by AMP and pyrophosphate.

Various mutants and truncated forms of the enzyme have been studied [Kumar89, Hill98, Meyer98, Meyer98a, Wu98, Ballicora07]. The N-terminal region appears to be required for allosteric regulation of the enzyme [Gardiol90, Wu01, Bejar06a, Ballicora07]. Co-expression of separately encoded N- and C-terminal domain polypeptides yields an active enzyme. The two domains interact strongly [Bejar04]. Residues Trp113 and Gln74 have been shown to be required for activation by fructose-1,6-bisphosphate [Figueroa11]. The Asp142 residue is important for catalytic activity [Frueauf01]. Homology modelling and site-directed mutagenesis allowed the identification of residues that play a role in binding of glucose-1-phosphate [Bejar06]. Further modeling and results from site-directed mutagenesis have led to a hypothesis for the mechanism of allosteric regulation of the enzyme [Figueroa11].

The homotetrameric subunit structure was determined using GlgC purified from E. coli B [Haugen76].

Under liquid culture conditions, mutations in glgC arise spontaneously and lead to contact-dependent growth inhibition of the ancestral glgC wild type strains [Lemonnier08].

Expression of GlgC is regulated at the transcriptional and translational level. Transcription of glgCAP is activated by cAMP and CRP as well as ppGpp [Romeo89, Romeo90] and PhoPQ under conditions of low Mg2+ concentration [Montero09, Montero10]. CsrA, the carbon storage regulator, binds to glgC mRNA and inhibits initiation of translation [Baker02].

Review: [Ballicora03]

Gene Citations: [Romeo88, Yang96b]

Locations: cytosol

Map Position: [3,566,056 <- 3,567,351] (76.86 centisomes)
Length: 1296 bp / 431 aa

Molecular Weight of Polypeptide: 48.698 kD (from nucleotide sequence), 49.0 kD (experimental) [Montero10 ]

Molecular Weight of Multimer: 185 kD (experimental) [Haugen76]

Unification Links: ASAP:ABE-0011204 , CGSC:708 , DIP:DIP-48147N , EchoBASE:EB0374 , EcoGene:EG10379 , EcoliWiki:b3430 , OU-Microarray:b3430 , PortEco:glgC , PR:PRO_000022777 , Pride:P0A6V1 , Protein Model Portal:P0A6V1 , RefSeq:NP_417888 , RegulonDB:EG10379 , SMR:P0A6V1 , String:511145.b3430 , UniProt:P0A6V1

Relationship Links: InterPro:IN-FAMILY:IPR005835 , InterPro:IN-FAMILY:IPR005836 , InterPro:IN-FAMILY:IPR011004 , InterPro:IN-FAMILY:IPR011831 , InterPro:IN-FAMILY:IPR023049 , Pfam:IN-FAMILY:PF00483 , Prosite:IN-FAMILY:PS00808 , Prosite:IN-FAMILY:PS00809 , Prosite:IN-FAMILY:PS00810

In Paralogous Gene Group: 264 (5 members)

Gene-Reaction Schematic: ?

Genetic Regulation Schematic: ?

GO Terms:

Biological Process: GO:0005978 - glycogen biosynthetic process Inferred from experiment Inferred by computational analysis [UniProtGOA12, UniProtGOA11, GOA01, Eydallin07]
GO:0005975 - carbohydrate metabolic process Inferred by computational analysis [UniProtGOA11]
GO:0005977 - glycogen metabolic process Inferred by computational analysis [UniProtGOA11]
GO:0008152 - metabolic process Inferred by computational analysis [UniProtGOA11]
GO:0009058 - biosynthetic process Inferred by computational analysis [GOA01]
Molecular Function: GO:0000287 - magnesium ion binding Inferred from experiment [Hill91]
GO:0008878 - glucose-1-phosphate adenylyltransferase activity Inferred from experiment Inferred by computational analysis [GOA01a, GOA01, Bejar06]
GO:0016208 - AMP binding Inferred from experiment [Hill91]
GO:0000166 - nucleotide binding Inferred by computational analysis [UniProtGOA11]
GO:0003824 - catalytic activity Inferred by computational analysis [UniProtGOA11]
GO:0005524 - ATP binding Inferred by computational analysis [UniProtGOA11]
GO:0016740 - transferase activity Inferred by computational analysis [UniProtGOA11]
GO:0016779 - nucleotidyltransferase activity Inferred by computational analysis [UniProtGOA11, GOA01]
Cellular Component: GO:0005737 - cytoplasm
GO:0005829 - cytosol Inferred by computational analysis [DiazMejia09]

MultiFun Terms: metabolism biosynthesis of macromolecules (cellular constituents) cytoplasmic polysaccharides

Essentiality data for glgC knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB enriched Yes 37 Aerobic 6.95   Yes [Gerdes03, Comment 1]
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 2]
M9 medium with 1% glycerol Yes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 3]
MOPS medium with 0.4% glucose Yes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 2]
Yes [Feist07, Comment 4]

Credits:
Last-Curated ? 20-Jul-2011 by Keseler I , SRI International


Enzymatic reaction of: glucose-1-phosphate adenylyltransferase

Synonyms: ADP-glucose synthase, ADP-glucose pyrophosphorylase, ADP:α-D-glucose-1-phosphate adenylyltransferase

EC Number: 2.7.7.27

α-D-glucose 1-phosphate + ATP + H+ <=> ADP-α-D-glucose + diphosphate

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

In Pathways: glycogen biosynthesis I (from ADP-D-Glucose)

Cofactors or Prosthetic Groups: Mg2+ [Hill91]

Activators (Allosteric): fructose 1,6-bisphosphate [Leung86, Gardiol90] , hexanediol 1,6-bisphosphate [Leung86]

Activators (Unknown Mechanism): pyridoxal 5'-phosphate [Gardiol90, Figueroa11]

Inhibitors (Allosteric): AMP [Hill91, Gardiol90]

Inhibitors (Unknown Mechanism): diphosphate [Preiss83]

Primary Physiological Regulators of Enzyme Activity: fructose 1,6-bisphosphate , AMP

Kinetic Parameters:

Substrate
Km (μM)
kcat (sec-1)
kcat/Km (sec-1 μM-1)
Citations
α-D-glucose 1-phosphate
17.0
[Bejar06, BRENDA14]
α-D-glucose 1-phosphate
40.0, 210.0
[Figueroa11, BRENDA14]
α-D-glucose 1-phosphate
390.0, 450.0, 920.0
[Ballicora02, BRENDA14]
α-D-glucose 1-phosphate
25.0
[Hill91]
ATP
155.0, 162.0, 300.0
[Ballicora02, BRENDA14]
ATP
320.0, 11000.0
[Figueroa11, BRENDA14]
ATP
590.0
370.0
[Bejar06, BRENDA14]
diphosphate
120.0
[Hill91]

T(opt): 37 °C [BRENDA14, Nagai09]

pH(opt): 7.5 [BRENDA14, Nagai09]


Sequence Features

Feature Class Location Citations Comment
Cleavage-of-Initial-Methionine 1
[Parsons78, UniProt11]
UniProt: Removed.
Chain 2 -> 431
[UniProt09]
UniProt: Glucose-1-phosphate adenylyltransferase;
Amino-Acid-Sites-That-Bind 39
[UniProt10a]
UniProt: Allosteric activator;
Extrinsic-Sequence-Variant 44
[UniProt10a]
Alternate sequence: A → T; UniProt: (in SG14 mutant; lower apparent affinities for substrates, the activator, F16BP and the inhibitor);
Extrinsic-Sequence-Variant 67
[UniProt10a]
Alternate sequence: R → C; UniProt: (in CL1136 mutant; less dependent on the allosteric activator, F16BP, for activity and less sensitive to inhibition by AMP);
Amino-Acid-Sites-That-Bind 114
[UniProt10a]
UniProt: Glucose-1-phosphate;
Sequence-Conflict 161
[Meyer92a, UniProt10a]
Alternate sequence: A → V; UniProt: (in Ref. 3; CAA23544/AAA98736/AAA23873);
Sequence-Conflict 166
[Meyer92a, UniProt10a]
Alternate sequence: A → V; UniProt: (in Ref. 3; CAA23544/AAA98736/AAA23873);
Sequence-Conflict 189
[Meyer92a, UniProt10a]
Alternate sequence: I → T; UniProt: (in Ref. 3; CAA23544/AAA98736/AAA23873);
Mutagenesis-Variant 195
[Hill91, UniProt11]
Alternate sequence: K → R; UniProt: No loss in enzyme activity.
Alternate sequence: K → Q; UniProt: No loss in enzyme activity.
Alternate sequence: K → H; UniProt: No loss in enzyme activity.
Alternate sequence: K → I; UniProt: No loss in enzyme activity.
Alternate sequence: K → E; UniProt: No loss in enzyme activity.
Amino-Acid-Sites-That-Bind 195
[UniProt10a]
UniProt: Glucose-1-phosphate;
Extrinsic-Sequence-Variant 295
[UniProt10a]
Alternate sequence: P → S; UniProt: (in SG5 mutant);
Sequence-Conflict 296
[Meyer92a, UniProt10a]
Alternate sequence: E → K; UniProt: (in Ref. 3; CAA23544/AAA98736);
Extrinsic-Sequence-Variant 336
[UniProt10a]
Alternate sequence: G → D; UniProt: (in 618 mutant; causes lowered affinity for AMP);


Gene Local Context (not to scale): ?

Transcription Units:

Notes:

History:
10/20/97 Gene b3430 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10379; confirmed by SwissProt match.


References

Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

Baker02: Baker CS, Morozov I, Suzuki K, Romeo T, Babitzke P (2002). "CsrA regulates glycogen biosynthesis by preventing translation of glgC in Escherichia coli." Mol Microbiol 44(6);1599-610. PMID: 12067347

Ballicora02: Ballicora MA, Sesma JI, Iglesias AA, Preiss J (2002). "Characterization of chimeric ADPglucose pyrophosphorylases of Escherichia coli and Agrobacterium tumefaciens. Importance of the C-terminus on the selectivity for allosteric regulators." Biochemistry 41(30);9431-7. PMID: 12135365

Ballicora03: Ballicora MA, Iglesias AA, Preiss J (2003). "ADP-glucose pyrophosphorylase, a regulatory enzyme for bacterial glycogen synthesis." Microbiol Mol Biol Rev 67(2);213-25, table of contents. PMID: 12794190

Ballicora07: Ballicora MA, Erben ED, Yazaki T, Bertolo AL, Demonte AM, Schmidt JR, Aleanzi M, Bejar CM, Figueroa CM, Fusari CM, Iglesias AA, Preiss J (2007). "Identification of regions critically affecting kinetics and allosteric regulation of the Escherichia coli ADP-glucose pyrophosphorylase by modeling and pentapeptide-scanning mutagenesis." J Bacteriol 189(14);5325-33. PMID: 17496097

Bejar04: Bejar CM, Ballicora MA, Gomez-Casati DF, Iglesias AA, Preiss J (2004). "The ADP-glucose pyrophosphorylase from Escherichia coli comprises two tightly bound distinct domains." FEBS Lett 573(1-3);99-104. PMID: 15327982

Bejar06: Bejar CM, Jin X, Ballicora MA, Preiss J (2006). "Molecular architecture of the glucose 1-phosphate site in ADP-glucose pyrophosphorylases." J Biol Chem 281(52);40473-84. PMID: 17079236

Bejar06a: Bejar CM, Ballicora MA, Iglesias AA, Preiss J (2006). "ADPglucose pyrophosphorylase's N-terminus: structural role in allosteric regulation." Biochem Biophys Res Commun 343(1);216-21. PMID: 16530732

BRENDA14: BRENDA team (2014). "Imported from BRENDA version existing on Aug 2014." http://www.brenda-enzymes.org.

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Eydallin07: Eydallin G, Moran-Zorzano MT, Munoz FJ, Baroja-Fernandez E, Montero M, Alonso-Casajus N, Viale AM, Pozueta-Romero J (2007). "An Escherichia coli mutant producing a truncated inactive form of GlgC synthesizes glycogen: further evidences for the occurrence of various important sources of ADPglucose in enterobacteria." FEBS Lett 581(23);4417-22. PMID: 17719034

Feist07: Feist AM, Henry CS, Reed JL, Krummenacker M, Joyce AR, Karp PD, Broadbelt LJ, Hatzimanikatis V, Palsson BO (2007). "A genome-scale metabolic reconstruction for Escherichia coli K-12 MG1655 that accounts for 1260 ORFs and thermodynamic information." Mol Syst Biol 3;121. PMID: 17593909

Figueroa11: Figueroa CM, Esper MC, Bertolo A, Demonte AM, Aleanzi M, Iglesias AA, Ballicora MA (2011). "Understanding the allosteric trigger for the fructose-1,6-bisphosphate regulation of the ADP-glucose pyrophosphorylase from Escherichia coli." Biochimie 93(10);1816-23. PMID: 21741429

Frueauf01: Frueauf JB, Ballicora MA, Preiss J (2001). "Aspartate residue 142 is important for catalysis by ADP-glucose pyrophosphorylase from Escherichia coli." J Biol Chem 276(49);46319-25. PMID: 11567027

Gardiol90: Gardiol A, Preiss J (1990). "Escherichia coli E-39 ADPglucose synthetase has different activation kinetics from the wild-type allosteric enzyme." Arch Biochem Biophys 280(1);175-80. PMID: 2162151

Gerdes03: Gerdes SY, Scholle MD, Campbell JW, Balazsi G, Ravasz E, Daugherty MD, Somera AL, Kyrpides NC, Anderson I, Gelfand MS, Bhattacharya A, Kapatral V, D'Souza M, Baev MV, Grechkin Y, Mseeh F, Fonstein MY, Overbeek R, Barabasi AL, Oltvai ZN, Osterman AL (2003). "Experimental determination and system level analysis of essential genes in Escherichia coli MG1655." J Bacteriol 185(19);5673-84. PMID: 13129938

GOA01: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA01a: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

Haugen76: Haugen TH, Ishaque A, Preiss J (1976). "Biosynthesis of bacterial glycogen. Characterization of the subunit structure of Escherichia coli B glucose-1-phosphate adenylyltransferase (EC 2.7.7.27)." J Biol Chem 251(24);7880-5. PMID: 826540

Hill91: Hill MA, Kaufmann K, Otero J, Preiss J (1991). "Biosynthesis of bacterial glycogen. Mutagenesis of a catalytic site residue of ADP-glucose pyrophosphorylase from Escherichia coli." J Biol Chem 266(19);12455-60. PMID: 1648099

Hill98: Hill MA, Preiss J (1998). "Functional analysis of conserved histidines in ADP-glucose pyrophosphorylase from Escherichia coli." Biochem Biophys Res Commun 244(2);573-7. PMID: 9514953

Joyce06: Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S (2006). "Experimental and computational assessment of conditionally essential genes in Escherichia coli." J Bacteriol 188(23);8259-71. PMID: 17012394

Kumar89: Kumar A, Ghosh P, Lee YM, Hill MA, Preiss J (1989). "Biosynthesis of bacterial glycogen. Determination of the amino acid changes that alter the regulatory properties of a mutant Escherichia coli ADP-glucose synthetase." J Biol Chem 264(18);10464-71. PMID: 2543670

Lemonnier08: Lemonnier M, Levin BR, Romeo T, Garner K, Baquero MR, Mercante J, Lemichez E, Baquero F, Blazquez J (2008). "The evolution of contact-dependent inhibition in non-growing populations of Escherichia coli." Proc Biol Sci 275(1630);3-10. PMID: 17956846

Leung86: Leung P, Lee YM, Greenberg E, Esch K, Boylan S, Preiss J (1986). "Cloning and expression of the Escherichia coli glgC gene from a mutant containing an ADPglucose pyrophosphorylase with altered allosteric properties." J Bacteriol 167(1);82-8. PMID: 3013841

Meyer92a: Meyer CR, Ghosh P, Remy E, Preiss J (1992). "Cloning, expression, and nucleotide sequence of a mutant glgC gene from Escherichia coli B." J Bacteriol 174(13);4509-12. PMID: 1320612

Meyer98: Meyer CR, Yirsa J, Gott B, Preiss J (1998). "A kinetic study of site-directed mutants of Escherichia coli ADP-glucose pyrophosphorylase: the role of residue 295 in allosteric regulation." Arch Biochem Biophys 352(2);247-54. PMID: 9587413

Meyer98a: Meyer CR, Bork JA, Nadler S, Yirsa J, Preiss J (1998). "Site-directed mutagenesis of a regulatory site of Escherichia coli ADP-glucose pyrophosphorylase: the role of residue 336 in allosteric behavior." Arch Biochem Biophys 353(1);152-9. PMID: 9578610

Montero09: Montero M, Eydallin G, Viale AM, Almagro G, Munoz FJ, Rahimpour M, Sesma MT, Baroja-Fernandez E, Pozueta-Romero J (2009). "Escherichia coli glycogen metabolism is controlled by the PhoP-PhoQ regulatory system at submillimolar environmental Mg2+ concentrations, and is highly interconnected with a wide variety of cellular processes." Biochem J 424(1);129-41. PMID: 19702577

Montero10: Montero M, Almagro G, Eydallin G, Viale AM, Munoz FJ, Bahaji A, Li J, Rahimpour M, Baroja-Fernandez E, Pozueta-Romero J (2010). "Escherichia coli glycogen genes are organized in a single glgBXCAP transcriptional unit possessing an alternative suboperonic promoter within glgC that directs glgAP expression." Biochem J 433(1);107-17. PMID: 21029047

Nagai09: Nagai YS, Sakulsingharoj C, Edwards GE, Satoh H, Greene TW, Blakeslee B, Okita TW (2009). "Control of starch synthesis in cereals: metabolite analysis of transgenic rice expressing an up-regulated cytoplasmic ADP-glucose pyrophosphorylase in developing seeds." Plant Cell Physiol 50(3);635-43. PMID: 19208694

Parsons78: Parsons TF, Preiss J (1978). "Biosynthesis of bacterial glycogen. Isolation and characterization of the pyridoxal-P allosteric activator site and the ADP-glucose-protected pyridoxal-P binding site of Escherichia coli B ADP-glucose synthase." J Biol Chem 253(21);7638-45. PMID: 359552

Preiss83: Preiss J, Greenberg E (1983). "Pyrophosphate may be involved in regulation of bacterial glycogen synthesis." Biochem Biophys Res Commun 115(3);820-6. PMID: 6312996

Romeo88: Romeo T, Kumar A, Preiss J (1988). "Analysis of the Escherichia coli glycogen gene cluster suggests that catabolic enzymes are encoded among the biosynthetic genes." Gene 70(2);363-76. PMID: 2975249

Romeo89: Romeo T, Preiss J (1989). "Genetic regulation of glycogen biosynthesis in Escherichia coli: in vitro effects of cyclic AMP and guanosine 5'-diphosphate 3'-diphosphate and analysis of in vivo transcripts." J Bacteriol 171(5);2773-82. PMID: 2468650

Romeo90: Romeo T, Black J, Preiss J (1990). "Genetic regulation of glycogen biosynthesis in Escherichia coli: In vivo effects of the catabolite represion and stringent response systems in glg gene expression." Curr Microbiol 21;131-137.

UniProt09: UniProt Consortium (2009). "UniProt version 15.8 released on 2009-10-01 00:00:00." Database.

UniProt10a: UniProt Consortium (2010). "UniProt version 2010-11 released on 2010-11-02 00:00:00." Database.

UniProt11: UniProt Consortium (2011). "UniProt version 2011-06 released on 2011-06-30 00:00:00." Database.

UniProtGOA11: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

UniProtGOA12: UniProt-GOA (2012). "Gene Ontology annotation based on UniPathway vocabulary mapping."

Wu01: Wu MX, Preiss J (2001). "Truncated forms of the recombinant Escherichia coli ADP-glucose pyrophosphorylase: the importance of the N-terminal region for allosteric activation and inhibition." Arch Biochem Biophys 389(2);159-65. PMID: 11339804

Wu98: Wu MX, Preiss J (1998). "The N-terminal region is important for the allosteric activation and inhibition of the Escherichia coli ADP-glucose pyrophosphorylase." Arch Biochem Biophys 358(1);182-8. PMID: 9750179

Yang96b: Yang H, Liu MY, Romeo T (1996). "Coordinate genetic regulation of glycogen catabolism and biosynthesis in Escherichia coli via the CsrA gene product." J Bacteriol 178(4);1012-7. PMID: 8576033

Other References Related to Gene Regulation

Bridger78: Bridger WA, Paranchych W (1978). "relA Gene control of bacterial glycogen synthesis." Can J Biochem 56(6);403-6. PMID: 352487

MedinaRivera11: Medina-Rivera A, Abreu-Goodger C, Thomas-Chollier M, Salgado H, Collado-Vides J, van Helden J (2011). "Theoretical and empirical quality assessment of transcription factor-binding motifs." Nucleic Acids Res 39(3);808-24. PMID: 20923783

Traxler08: Traxler MF, Summers SM, Nguyen HT, Zacharia VM, Hightower GA, Smith JT, Conway T (2008). "The global, ppGpp-mediated stringent response to amino acid starvation in Escherichia coli." Mol Microbiol 68(5);1128-48. PMID: 18430135


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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
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