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discounted EARLY registration ends Dec 31, 2014
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Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
12/28 - 12/31
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MetaCyc Enzyme: guanylate kinase

Gene: gmk Accession Numbers: EG10965 (MetaCyc), b3648, ECK3638

Synonyms: spoR, GMP kinase

Species: Escherichia coli K-12 substr. MG1655

Subunit composition of guanylate kinase = [Gmk]2
         guanylate kinase = Gmk

Summary:
Nucleotide monophosphate kinases are important enzymes in the maintenance of nucleotide pools. They are specific for the nucleobase of the phosphate acceptor substrate. They belong to the nucleoside monophosphate kinase (NMPK) superfamily The product of gene gmk reversibly transfers the γ-phosphoryl group of the nucleoside triphosphate donor (ATP) to the acceptor nucleoside monophosphate (GMP or dGMP) to produce the corresponding nucleoside diphosphate (GDP or dGDP) and ADP [Hible05].

The E. coli K-12 enzyme is multimeric, and its protomeric state is determined by ionic strength conditions. Under high ionic strength the enzyme is a dimer of 43 kDa and under low ionic strength the enzyme is a tetramer of 92.5 kDa. Tetramerization lowers the level of interaction between binding sites and decreases the total activity [Gentry93a]. Later structural and calorimetric studies showed E. coli Gmk to be in equilibrium between a dimeric and a hexameric form, which shifts to the dimeric form under physiological conditions. The hexamer was observed in four different crystal forms [Hible05, Hible06].

The human enzyme is a target for chemotherapeutic agents and also plays a role in activation of antiviral and antineoplastic drugs [Stolworthy03]. The bacterial enzyme is of interest as a drug target. The crystal structure of the E. coli enzyme has been used as a model for these applications [Hible06]. A novel, conditional guanylate kinase-deficient strain of E. coli strain has been constructed for use in the evaluation of drug activation by this enzyme and to identify drug-resistant variants [Stolworthy03].

Review: Review: Jensen, K.F., G. Dandanell, B. Hove-Jensen, and M. Willemoes (2008) "Nucleotides, Nucleosides and Nucleobases" EcoSal 3.6.2 [ECOSAL]

Locations: cytosol

Map Position: [3,819,451 -> 3,820,074]

Molecular Weight of Polypeptide: 23.593 kD (from nucleotide sequence), 23.462 kD (experimental) [Hible05 ]

Molecular Weight of Multimer: 43.0 kD (experimental) [Gentry93a]

pI: 6.46

Unification Links: ASAP:ABE-0011930 , CGSC:33871 , EchoBASE:EB0958 , EcoGene:EG10965 , EcoliWiki:b3648 , Mint:MINT-1286577 , ModBase:P60546 , OU-Microarray:b3648 , PortEco:gmk , Pride:P60546 , Protein Model Portal:P60546 , RefSeq:NP_418105 , RegulonDB:EG10965 , SMR:P60546 , String:511145.b3648 , UniProt:P60546

Relationship Links: InterPro:IN-FAMILY:IPR008144 , InterPro:IN-FAMILY:IPR008145 , InterPro:IN-FAMILY:IPR017665 , InterPro:IN-FAMILY:IPR020590 , InterPro:IN-FAMILY:IPR027417 , PDB:Structure:1S96 , PDB:Structure:2AN9 , PDB:Structure:2ANB , PDB:Structure:2ANC , PDB:Structure:2F3R , PDB:Structure:2F3T , Pfam:IN-FAMILY:PF00625 , Prosite:IN-FAMILY:PS00856 , Prosite:IN-FAMILY:PS50052 , Smart:IN-FAMILY:SM00072

Gene-Reaction Schematic: ?

GO Terms:

Biological Process: GO:0046939 - nucleotide phosphorylation Inferred by computational analysis Inferred from experiment [Gentry93a, GOA06, GOA01a, GOA01]
GO:0006163 - purine nucleotide metabolic process Inferred by computational analysis [GOA06, GOA01]
GO:0016310 - phosphorylation Inferred by computational analysis [UniProtGOA11a]
Molecular Function: GO:0004385 - guanylate kinase activity Inferred from experiment Inferred by computational analysis [GOA06, GOA01a, GOA01, Gentry93a]
GO:0042802 - identical protein binding Inferred from experiment [Hible05, Gentry93a]
GO:0000166 - nucleotide binding Inferred by computational analysis [UniProtGOA11a]
GO:0005524 - ATP binding Inferred by computational analysis [UniProtGOA11a, GOA06]
GO:0016301 - kinase activity Inferred by computational analysis [UniProtGOA11a]
GO:0016740 - transferase activity Inferred by computational analysis [UniProtGOA11a]
Cellular Component: GO:0005829 - cytosol Inferred from experiment Inferred by computational analysis [DiazMejia09, Ishihama08]
GO:0005737 - cytoplasm Inferred by computational analysis [UniProtGOA11, UniProtGOA11a, GOA06]

MultiFun Terms: metabolism biosynthesis of building blocks nucleotides purine ribonucleotide biosynthesis
metabolism central intermediary metabolism nucleotide and nucleoside conversions

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International


Enzymatic reaction of: guanylate kinase

Synonyms: GMP kinase, ATP:(d)GMP phosphotransferase, 5'-guanylate kinase

EC Number: 2.7.4.8

ATP + GMP <=> ADP + GDP

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

This reaction is reversible. [Hible05]

Alternative Substrates for GMP [Comment 1 ]: dGMP [Oeschger66 ] , IMP [Oeschger66 ]

Alternative Substrates for ATP [Comment 1 ]: dATP [Oeschger66 ] , GTP [Oeschger66 ]

In Pathways: superpathway of histidine, purine, and pyrimidine biosynthesis , superpathway of purine nucleotides de novo biosynthesis II , superpathway of guanosine nucleotides de novo biosynthesis II , superpathway of guanosine nucleotides de novo biosynthesis I , guanosine ribonucleotides de novo biosynthesis

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International

Summary:
The data from [Oeschger66] are for E. coli B. Some assays described in this publication utilized dGMP as substrate.

Guanylate kinase from E. coli K-12 showed a positive cooperativity for GDP synthesis, with a sigmoidal response to GMP concentration [Gentry93a]. However, later work did not show cooperativity toward GMP [Hible05].

Cofactors or Prosthetic Groups [Comment 2]: Mg2+ [Oeschger66]

Activators (Unknown Mechanism): K+ [Oeschger66] , ammonium [Oeschger66]

Inhibitors (Competitive): dGTP [Oeschger66, Comment 3] , GTP [Oeschger66, Comment 3] , GDP [Oeschger66, Comment 3] , guanosine [Oeschger66]

Inhibitors (Unknown Mechanism): dXMP [Oeschger66] , IMP [Oeschger66] , AMP [Oeschger66]


Enzymatic reaction of: deoxyguanylate kinase

ATP + dGMP <=> ADP + dGDP

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

This reaction is reversible. [Oeschger66]

In Pathways: purine deoxyribonucleosides salvage

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International

Summary:
The data from [Oeschger66] are for E. coli B. Guanylate kinase was shown to be highly specific for both GMP and dGMP. ATP and dATP were the preferred phosphoryl donors with relative rates of 100% and 84% respectively for dGMP phosphorylation. The relative rate for GTP was 1.5% and CTP was ineffective [Oeschger66].

The catalytic rate of dGMP phosphorylation was reported to be 30% of the rate of GMP phosphorylation [Hible06].

pH(opt): 7.3-8.2 [Oeschger66]


Sequence Features

Feature Class Location Citations Comment
Conserved-Region 4 -> 184
[UniProt09]
UniProt: Guanylate kinase-like;
Nucleotide-Phosphate-Binding-Region 11 -> 18
[UniProt10]
UniProt: ATP; Non-Experimental Qualifier: by similarity;

History:
10/20/97 Gene b3648 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10965.


References

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

ECOSAL: EcoSal "Escherichia coli and Salmonella: Cellular and Molecular Biology." Online edition.

Gentry93a: Gentry D, Bengra C, Ikehara K, Cashel M (1993). "Guanylate kinase of Escherichia coli K-12." J Biol Chem 1993;268(19);14316-21. PMID: 8390989

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.

GOA06: GOA, SIB (2006). "Electronic Gene Ontology annotations created by transferring manual GO annotations between orthologous microbial proteins."

Hible05: Hible G, Renault L, Schaeffer F, Christova P, Zoe Radulescu A, Evrin C, Gilles AM, Cherfils J (2005). "Calorimetric and crystallographic analysis of the oligomeric structure of Escherichia coli GMP kinase." J Mol Biol 352(5);1044-59. PMID: 16140325

Hible06: Hible G, Daalova P, Gilles AM, Cherfils J (2006). "Crystal structures of GMP kinase in complex with ganciclovir monophosphate and Ap5G." Biochimie 88(9);1157-64. PMID: 16690197

Ishihama08: Ishihama Y, Schmidt T, Rappsilber J, Mann M, Hartl FU, Kerner MJ, Frishman D (2008). "Protein abundance profiling of the Escherichia coli cytosol." BMC Genomics 9;102. PMID: 18304323

Oeschger66: Oeschger MP, Bessman MJ (1966). "Purification and properties of guanylate kinase from Escherichia coli." J Biol Chem 1966;241(22);5452-60. PMID: 5333666

Oeschger78: Oeschger MP (1978). "Guanylate kinase from Escherichia coli B." Methods Enzymol 1978;51;473-82. PMID: 211389

Stolworthy03: Stolworthy TS, Krabbenhoft E, Black ME (2003). "A novel Escherichia coli strain allows functional analysis of guanylate kinase drug resistance and sensitivity." Anal Biochem 322(1);40-7. PMID: 14705778

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

UniProt10: UniProt Consortium (2010). "UniProt version 2010-07 released on 2010-06-15 00:00:00." Database.

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

UniProtGOA11a: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Sat Dec 20, 2014, BIOCYC13A.