Information on EC 2.7.4.8 - guanylate kinase

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY
2.7.4.8
-
RECOMMENDED NAME
GeneOntology No.
guanylate kinase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
ATP + GMP = ADP + GDP
show the reaction diagram
-
-
-
-
ATP + GMP = ADP + GDP
show the reaction diagram
conformational changes and induced-fit reaction mechanism of the allosteric enzyme, overview
-, P0A5I4
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
phospho group transfer
-
-
-
-
phospho group transfer
-
-
phospho group transfer
Escherichia coli TS202A
-
-
-
Phosphorylation
-
-
Phosphorylation
P60546
catalyzes the phosphorylation of GMP or dGMP
Phosphorylation
-, P0A5I4
-
PATHWAY
KEGG Link
MetaCyc Link
guanosine ribonucleotides de novo biosynthesis
-
Metabolic pathways
-
Purine metabolism
-
SYSTEMATIC NAME
IUBMB Comments
ATP:(d)GMP phosphotransferase
dGMP can also act as acceptor, and dATP can act as donor.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5'-GMP kinase
-
-
-
-
apo-EcGMPK
-
-
ATP: GMP phosphotransferase
-
-
ATP:GMP phosphotransferase
-
-
-
-
ATP:GMP phosphotransferase
-
-
CASK polypeptide
O14936
cf. EC 2.7.11.1, the protein contains a guanylate kinase domain
Cavbeta1b
-
-
Cavbeta2a
Q8VGC3
-
deoxyguanylate kinase
-
-
-
-
DLG1/SAP97
-
-
DLG1/SAP97
Q62696
-
GMK
Escherichia coli TS202A
-
-
-
GMP kinase
-
-
-
-
GMP kinase
-
-
guanosine monophosphate kinase
-
-
-
-
guanosine monophosphate kinase
-
-
guanosine monophosphate kinase (EcGMPK)
-
-
guanylate kinase
-
-
guanylate kinase
Escherichia coli TS202A
-
-
-
guanylate kinase
-
-
guanylate kinase
-
-
guanylate kinase
-
-
guanylate kinase
-
-
guanylate kinase (GK)
-
-
guanylate monophosphate kinase
-
-
kinase, guanylate (phosphorylating)
-
-
-
-
MAGUK
-
-
MAGUK
Q62696
-
MAGUK PSD-95
-
-
membrane associated guanylate kinase
-
-
membrane associated guanylate kinase protein
-
-
membrane-associated guanylate kinase
-
-
membrane-associated guanylate kinase
-
-
membrane-associated guanylate kinase
Q62696
-
membrane-associated guanylate kinase
-
-
post-synaptic density-95 membrane associated guanylate kinase
-
-
postsynaptic density protein-95 SH3 GK
-
-
PSD-95 GK
-
-
PSD-95 MAGUK
-
-
PSD-95alpha
-
-
PSD-95beta
-
-
Staphylococcus aureus guanylate monophosphate kinase
-
-
voltage-gated calcium channel beta1b
-
-
voltage-gated calcium channel beta2a
Q8VGC3
-
membrane-associated guanylate kinases
-
-
additional information
-
the enzyme belongs to the post-synaptic density-95 membrane associated guanylate kinase, MAGUK, family of scaffolding proteins,
CAS REGISTRY NUMBER
COMMENTARY
9026-59-9
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
calf
-
-
Manually annotated by BRENDA team
strain B
-
-
Manually annotated by BRENDA team
strain JE24F+, derived from W3110, uninfected or infected with RNA-phage MS2
-
-
Manually annotated by BRENDA team
strain K12
Uniprot
Manually annotated by BRENDA team
strain TS202A, guanylate-kinase-deficient
-
-
Manually annotated by BRENDA team
Escherichia coli JE24F+
strain JE24F+, derived from W3110, uninfected or infected with RNA-phage MS2
-
-
Manually annotated by BRENDA team
Escherichia coli K12
strain K12
Uniprot
Manually annotated by BRENDA team
Escherichia coli TS202A
strain TS202A, guanylate-kinase-deficient
-
-
Manually annotated by BRENDA team
Jerusalem artichoke
-
-
Manually annotated by BRENDA team
CASK polypeptide, cf. EC 2.7.11.1
SwissProt
Manually annotated by BRENDA team
mouse
-
-
Manually annotated by BRENDA team
strain H37Rv, Rv1389c gene
UniProt
Manually annotated by BRENDA team
nuclear gene VIRESCENT 2 or v2
-
-
Manually annotated by BRENDA team
Cavbeta2a
UniProt
Manually annotated by BRENDA team
female Fischer or male Buffalo rats
-
-
Manually annotated by BRENDA team
baker's yeast
-
-
Manually annotated by BRENDA team
RCSB Protein Data Bank: 1EX6, enzyme with a non-acetylated N terminus in its unligated form; RCSB Protein Data Bank: 1EX7, enzyme with a non-acetylated N terminus in a complex with GMP
Uniprot
Manually annotated by BRENDA team
pig
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
physiological function
-
guanylate kinase is the sole molecular target for the development of acquired resistance to the cytotoxic nucleotide 9-[2-(phosphonomethoxyethyl)]-guanine
physiological function
-
the guanylate kinase domain of DLG1/SAP97 binds to asymmetric cell division regulatory protein LGN in a phosphorylation-dependent manner
physiological function
Q62696
the guanylate kinase domain of DLG1/SAP97 binds to asymmetric cell division regulatory protein LGN in a phosphorylation-dependent manner
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
aciclovir (ACV-MP)
?
show the reaction diagram
-
-
-
-
?
ATP + (R)-3-((2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy)-4-hydroxybutylphosphonic acid
(R)-ganciclovir phosphonate monophosphate
show the reaction diagram
-
i.e. R-ganciclovir phosphonate, (S) enantiomer 100fold less efficient, used for racemic resolution
-
?
ATP + 6-thioguanosine 5'-monophosphate
ADP + 8-thioguanosine 5'-diphosphate
show the reaction diagram
-
-
-
-
?
ATP + 6-thioguanosine 5'-monophosphate
ADP + 8-thioguanosine 5'-diphosphate
show the reaction diagram
-
not thiodeoxyguanosine derivative
-
-
?
ATP + 8-azaguanosine 5'-monophosphate
ADP + 8-azaguanosine 5'-diphosphate
show the reaction diagram
-
-
-
-
?
ATP + 8-azaguanosine 5'-monophosphate
ADP + 8-azaguanosine 5'-diphosphate
show the reaction diagram
-
-
-
-
?
ATP + 8-azaguanosine 5'-monophosphate
ADP + 8-azaguanosine 5'-diphosphate
show the reaction diagram
-
-
-
-
?
ATP + 8-bromoguanosine 5'-monophosphate
ADP + 8-bromoguanosine 5'-diphosphate
show the reaction diagram
-
poor substrate
-
-
?
ATP + 9-(1,3-dihydroxy-2-propoxymethyl)guanine 5'-monophosphate
ADP + 9-(1,3-dihydroxy-2-propoxymethyl)guanine 5'-diphosphate
show the reaction diagram
-
no substrate: 9-(5,5-difluoro-5-phosphonopentyl)guanine 5'-monophosphate
-
-
?
ATP + 9-(2-hydroxyethoxymethyl)guanine 5'-monophosphate
ADP + 9-(2-hydroxyethoxymethyl)guanine 5'-diphosphate
show the reaction diagram
-
i.e. acyclovir 5'-monophosphate
-
-
?
ATP + 9-(5-phosphonopenthyl)guanine
?
show the reaction diagram
-
9-(5,5'-difluoro-5-phosphonopenthyl)guanine is not a substrate
-
-
?
ATP + AMP
ADP + ADP
show the reaction diagram
-
very low activity with AMP
-
-
?
ATP + dGMP
ADP + dGDP
show the reaction diagram
-
-
-
-
-
ATP + dGMP
ADP + dGDP
show the reaction diagram
-
-
-
-
r
ATP + dGMP
ADP + dGDP
show the reaction diagram
-
-
-
r
ATP + dGMP
ADP + dGDP
show the reaction diagram
-
-
-
-
r
ATP + dGMP
ADP + dGDP
show the reaction diagram
P60546
-
-
-
r
ATP + dGMP
ADP + dGDP
show the reaction diagram
-
-
-
-
r
ATP + dGMP
ADP + dGDP
show the reaction diagram
-
-
-
-
r
ATP + dGMP
ADP + dGDP
show the reaction diagram
-
-
-
-
r
ATP + dGMP
ADP + dGDP
show the reaction diagram
-
-
-
-
r
ATP + dGMP
ADP + dGDP
show the reaction diagram
-
-
-
-
r
ATP + dGMP
ADP + dGDP
show the reaction diagram
-
-
-
-
?
ATP + dGMP
ADP + dGDP
show the reaction diagram
-
phosphorylation at 48% the rate of GMP
-
r
ATP + dGMP
ADP + dGDP
show the reaction diagram
-
low activity, dGMP acts also as inhibitor
-
-
?
ATP + dGMP
ADP + dGDP
show the reaction diagram
-
dGMP is a poor substrate, the Kcat for dGMP is about 22fold lower than that observed for GMP. The value of kcat/Km for dGMP is at least 70fold lower than that of GMP
-
-
?
ATP + dGMP
ADP + dGDP
show the reaction diagram
Escherichia coli JE24F+
-
-
-
-
r
ATP + ganciclovir
ADP + ganciclovir phosphate
show the reaction diagram
-
-
-
-
?
ATP + ganciclovir monophosphate
?
show the reaction diagram
-
-
-
-
?
ATP + GDP
ADP + GTP
show the reaction diagram
Q16774
-
-
?
ATP + GDP
ADP + GTP
show the reaction diagram
-
-
-
-
-
ATP + GDP
ADP + GMP
show the reaction diagram
Q16774
-
-
?
ATP + GDP
ADP + guanosine 5'-tetraphosphate
show the reaction diagram
Q16774
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
-
-
-
-
ATP + GMP
ADP + GDP
show the reaction diagram
-
-
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
P60546
-
-
-
r
ATP + GMP
ADP + GDP
show the reaction diagram
-
-
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
-
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
-
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
-
-
r
ATP + GMP
ADP + GDP
show the reaction diagram
-
-
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
-
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
-
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
specificity
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
specificity
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
specificity
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
specificity
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
specificity
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
specificity
-
-
?, r
ATP + GMP
ADP + GDP
show the reaction diagram
-
best substrates
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
best substrates
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
best substrates
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
nucleoside monophosphate binding site is highly specific for guanine moiety
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
deoxyguanosine, guanosine are no acceptor substrates
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
deoxyguanosine, guanosine are no acceptor substrates
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
deoxyguanosine, guanosine are no acceptor substrates
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
no donor substrates are ITP, dGTP, dCTP or dTTP
-
-
?, r
ATP + GMP
ADP + GDP
show the reaction diagram
-
TMP is not an acceptor substrate
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
dCMP is no acceptor substrate
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
dCMP is no acceptor substrate
-
-
?, r
ATP + GMP
ADP + GDP
show the reaction diagram
-
IMP is no acceptor substrate
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
IMP is no acceptor substrate
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
6-thio-IMP is no acceptor substrate
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
XMP is no acceptor substrate
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
XMP is no acceptor substrate
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
XMP is no acceptor substrate
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
XMP is no acceptor substrate
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
dTMP is no acceptor substrate
-
-
?, r
ATP + GMP
ADP + GDP
show the reaction diagram
-
AMP is no acceptor substrate
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
AMP is no acceptor substrate
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
AMP is no acceptor substrate
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
AMP is no acceptor substrate
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
AMP is no acceptor substrate
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
AMP is no acceptor substrate
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
AMP is no acceptor substrate
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
AMP is no acceptor substrate
-
-
?, r
ATP + GMP
ADP + GDP
show the reaction diagram
-
dAMP is no acceptor substrate
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
dAMP is no acceptor substrate
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
dAMP is no acceptor substrate
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
dAMP is no acceptor substrate
-
-
?, r
ATP + GMP
ADP + GDP
show the reaction diagram
-
no donor substrates are GTP, CTP, UTP
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
no donor substrates are GTP, CTP, UTP
-
-
?, r
ATP + GMP
ADP + GDP
show the reaction diagram
P15454
GMP binding induces conformational changes in non-acetylated N-terminus mutants
-
-
-
ATP + GMP
ADP + GDP
show the reaction diagram
-
two specific binding sites: ATP- and GMP-binding site
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
CMP, UMP are no acceptor substrates
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
CMP, UMP are no acceptor substrates
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
CMP, UMP are no acceptor substrates
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
CMP, UMP are no acceptor substrates
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
CMP, UMP are no acceptor substrates
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
CMP, UMP are no acceptor substrates
-
-
?, r
ATP + GMP
ADP + GDP
show the reaction diagram
-
signal transduction
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
key enzyme of biosynthetic pathway of GTP or dGTP
-
r
ATP + GMP
ADP + GDP
show the reaction diagram
-
first step in 'cGMP-cycle' toward re-synthesis of cGMP
-
-
-
ATP + GMP
ADP + GDP
show the reaction diagram
-
regulation of cellular adhesion and signal transduction at sites of cell-cell contact
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
CASK construct has no activity, PSD-95 construct has no activity
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-, P0A5I4
guanylate kinase is an essential enzyme
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-, P0A5I4
upon substrate binding, the LID and nucleotide-monophosphate-binding domains are brought together and toward the CORE with large concerted movements about the alpha3, helix 3, axis
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
Escherichia coli JE24F+
-
-
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
Escherichia coli TS202A
-
signal transduction
-
-
?
ATP + IMP
ADP + IDP
show the reaction diagram
-
not
-
-
-
ATP + IMP
ADP + IDP
show the reaction diagram
-
very poor substrate
-
-
?
dATP + dGMP
dADP + dGDP
show the reaction diagram
-
-
-
?
dATP + dGMP
dADP + dGDP
show the reaction diagram
-
-
-
-
?
dATP + dGMP
dADP + dGDP
show the reaction diagram
-
-
-
-
?
dATP + dGMP
dADP + dGDP
show the reaction diagram
-
-
-
-
?
dATP + dGMP
dADP + dGDP
show the reaction diagram
-
-
-
-
?
dATP + dGMP
dADP + dGDP
show the reaction diagram
-
-
-
-
?
dATP + dGMP
dADP + dGDP
show the reaction diagram
-
as good as ATP
-
-
?
dATP + dGMP
dADP + dGDP
show the reaction diagram
-
phosphorylation at 22% the rate of ATP
-
?
dATP + GMP
dADP + GDP
show the reaction diagram
-
-
-
?
dATP + GMP
dADP + GDP
show the reaction diagram
-
-
-
-
?
dATP + GMP
dADP + GDP
show the reaction diagram
-
-
-
-
?
dATP + GMP
dADP + GDP
show the reaction diagram
-
-
-
-
?
dATP + GMP
dADP + GDP
show the reaction diagram
-
-
-
-
?
dATP + GMP
dADP + GDP
show the reaction diagram
-
as good as ATP
-
-
?
dATP + GMP
dADP + GDP
show the reaction diagram
-
phosphorylation at 81% the rate of ATP
-
?
dGMP + ATP
dGDP + ADP
show the reaction diagram
-
-
-
-
-
dGMP + ATP
dGDP + ADP
show the reaction diagram
-
-
-
-
?
dGMP + ATP
dGDP + ADP
show the reaction diagram
P60546
GMPKs catalyze the reversible phosphorylation of GMP and dGMP to their diphosphate form in the cell using ATP as a preferred phosphate donor.
-
-
r
dGMP + ATP
dGDP + ADP
show the reaction diagram
-
Catalyses reversible phosphoryl transfer from a nucleotide donor to a nucleotide acceptor. Phosphorylation of (d)GMP to (d)GDP using ATP as phosphoryl donor. Guanylate monophosphate kinases are involved in the synthesis of nucleotide precursors, they indirectly modulate the synthesis of DNA and RNA.
-
-
r
GMP + ATP
GDP + ADP
show the reaction diagram
-
-
-
-
-
GMP + ATP
GDP + ADP
show the reaction diagram
-
-
-
-
?
GMP + ATP
GDP + ADP
show the reaction diagram
P60546
GMPKs catalyze the reversible phosphorylation of GMP and dGMP to their diphosphate form in the cell using ATP as a preferred phosphate donor.
-
-
r
GMP + ATP
GDP + ADP
show the reaction diagram
-
Catalyses reversible phosphoryl transfer from a nucleotide donor to a nucleotide acceptor. Phosphorylation of (d)GMP to (d)GDP using ATP as phosphoryl donor. Guanylate monophosphate kinases are involved in the synthesis of nucleotide precursors, they indirectly modulate the synthesis of DNA and RNA.
-
-
r
GMP + MgATP2-
MgADP- + GDP
show the reaction diagram
-
-
-
-
-
GMP + MgATP2-
MgADP- + GDP
show the reaction diagram
-
-
-
-
?
guanosine monophosphate + adenosine triphosphate
guanosine diphosphate + adenosine diphosphate
show the reaction diagram
-, P0A5I4
Guanylate kinase (GK) is an essential enzyme that catalyzes the transfer of a phosphate from adenosine triphosphate (ATP) to guanosine monophosphate (GMP).
-
-
?
guanosine monophosphate + adenosine triphosphate
guanosine diphosphate + adenosine diphosphate
show the reaction diagram
Q92GC9, -
in the presence of Mg2+
-
-
r
additional information
?
-
-
MAGUKs contain three PSD-95/Discs large/Zona occludens 1, i.e. PDZ, domains, an src-homology 3, i.e. SH3, domain and a C-terminal guanylate kinase domain and play a key role in the regulation of the intracellular trafficking and synaptic localization of ionotropic glutamate receptors. In particular, the postsynaptic density-95-like subfamily of MAGUKs, PSD-MAGUKs, organizes ionotropic glutamate receptors and their associated signaling proteins in the postsynaptic density of the excitatory synapse regulating the strength of synaptic activity. Alterations of PSD-MAGUK protein interaction with N-methyl-D-aspartate, NMDA, receptors regulatory subunits are common events in several CNS disorders, overview, NMDA receptors' synaptic localization and binding to PSD-MAGUK protein family play a key role in the control of downstream signals resulting from receptor activation, physiological function, overview
-
-
-
additional information
?
-
-
MAGUKs contain three PSD-95/Discs large/Zona occludens 1, i.e. PDZ, domains, an src-homology 3, i.e. SH3, domain and a C-terminal guanylate kinase domain and play a key role in the regulation of the intracellular trafficking and synaptic localization of ionotropic glutamate receptors. In particular, the postsynaptic density-95-like subfamily of MAGUKs, PSD-MAGUKs, organizes ionotropic glutamate receptors and their associated signaling proteins in the postsynaptic density of the excitatory synapse regulating the strength of synaptic activity. Alterations of PSD-MAGUK protein interaction with N-methyl-D-aspartate, NMDA, receptors regulatory subunits are common events in several CNS disorders, overview. NMDA receptors' synaptic localization and binding to PSD-MAGUK protein family play a key role in the control of downstream signals resulting from receptor activation, physiological function, overview. The enzyme plays a role in excitotoxicity and neurodegenerative disorders, e.g. in Parkinson disease and Alzheimer disease. Physiological functions, detailed overview
-
-
-
additional information
?
-
-
synaptic scaffolding molecule, S-SCAM, is a synaptic protein, which harbors five or six PSD-95/Discs large/ZO-1, a guanylate kinase, and two WW domains. S-SCAM is associated with beta-DG and neuroligin 2 at inhibitory synapses, and functions as a linker between the dystrophin glycoprotein complex and the neurexin-neuroligin complex, complex formation analysis, overview
-
-
-
additional information
?
-
-
the cytosolic isozyme is indispensable for the growth and development of plants, but not for chloroplast development, while the plastid/mitochondrial isozyme is is essential for chloroplast differentiation, overview
-
-
-
additional information
?
-
-
the post-synaptic density-95 membrane associated guanylate kinase family of scaffolding proteins, MAGUK, associate with N-methyl-D-aspartate receptor NR2 subunits via their C-terminal glutamate serine, or aspartate/glutamate, valine motifs. N-methyl-D-aspartate receptors are a subclass of ionotropic glutamate receptors that are trafficked and/or clustered at synapses by MAGUK. Receptor binding of PSD variants differin the impact on the stabilisation, turnover and compartmentalisation of N-methyl-D-aspartate receptor subtypes in neurones during development and in the mature brain
-
-
-
additional information
?
-
Q8VGC3
the voltage-gated calcium channel beta1b contains a conserved guanylate kinase domain, which is alone recapitulating calcium channel beta-subunit CaVbeta-mediated modulation of channel activation facilitating inactivation of the voltage-gated channel. CaVbeta can switch the inactivation phenotype conferred to CaV2.3 from slow to fast after posttranslational modifications during channel biogenesis, modulation mechanism, overview, the voltage-gated calcium channel beta2a contains a conserved guanylate kinase domain, which is alone recapitulating calcium channel beta-subunit CaVbeta-mediated modulation of channel activation inhibiting inactivation of the voltage-gated channel. CaVbeta can switch the inactivation phenotype conferred to CaV2.3 from slow to fast after posttranslational modifications during channel biogenesis, modulation mechanism, overview
-
-
-
additional information
?
-
-
binding of N-methyl-D-aspartate receptors NR2B and NR2A, wild-type and mutant proteins, by PSD variants, overview
-
-
-
additional information
?
-
-
guanylate kinase binds a fragment of microtubule-associated protein-1a, i.e. MAP1a, in the GMP-binding site, the minimal GK binding site comprised by residues 1862-1878. MAP1a, which helps remodel the microtubule cytoskeleton in an activity-dependent manner, a is a common binding partner of PSD-95 GK and binds GK in an extended conformation, PSD-95 GK ligand consensus is not strongly constrained, binding via binding intermediate, structure, molecular dynamics simulation, overview
-
-
-
additional information
?
-
-
no activity with CMP, dTMP, dAMP, dCMP, and UMP
-
-
-
additional information
?
-
-, P0A5I4
the enzyme forms complexes with DNA
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
aciclovir (ACV-MP)
?
show the reaction diagram
-
-
-
-
?
ATP + dGMP
ADP + dGDP
show the reaction diagram
P60546
-
-
-
r
ATP + dGMP
ADP + dGDP
show the reaction diagram
-
-
-
-
?
ATP + ganciclovir
ADP + ganciclovir phosphate
show the reaction diagram
-
-
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
P60546
-
-
-
r
ATP + GMP
ADP + GDP
show the reaction diagram
-
-
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
-
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
signal transduction
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-
key enzyme of biosynthetic pathway of GTP or dGTP
-
r
ATP + GMP
ADP + GDP
show the reaction diagram
-
first step in 'cGMP-cycle' toward re-synthesis of cGMP
-
-
-
ATP + GMP
ADP + GDP
show the reaction diagram
-
regulation of cellular adhesion and signal transduction at sites of cell-cell contact
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
-, P0A5I4
guanylate kinase is an essential enzyme
-
-
?
ATP + GMP
ADP + GDP
show the reaction diagram
Escherichia coli TS202A
-
signal transduction
-
-
?
dGMP + ATP
dGDP + ADP
show the reaction diagram
-
-
-
-
-
dGMP + ATP
dGDP + ADP
show the reaction diagram
-
-
-
-
?
dGMP + ATP
dGDP + ADP
show the reaction diagram
P60546
GMPKs catalyze the reversible phosphorylation of GMP and dGMP to their diphosphate form in the cell using ATP as a preferred phosphate donor.
-
-
r
GMP + ATP
GDP + ADP
show the reaction diagram
-
-
-
-
-
GMP + ATP
GDP + ADP
show the reaction diagram
-
-
-
-
?
GMP + ATP
GDP + ADP
show the reaction diagram
P60546
GMPKs catalyze the reversible phosphorylation of GMP and dGMP to their diphosphate form in the cell using ATP as a preferred phosphate donor.
-
-
r
additional information
?
-
-
MAGUKs contain three PSD-95/Discs large/Zona occludens 1, i.e. PDZ, domains, an src-homology 3, i.e. SH3, domain and a C-terminal guanylate kinase domain and play a key role in the regulation of the intracellular trafficking and synaptic localization of ionotropic glutamate receptors. In particular, the postsynaptic density-95-like subfamily of MAGUKs, PSD-MAGUKs, organizes ionotropic glutamate receptors and their associated signaling proteins in the postsynaptic density of the excitatory synapse regulating the strength of synaptic activity. Alterations of PSD-MAGUK protein interaction with N-methyl-D-aspartate, NMDA, receptors regulatory subunits are common events in several CNS disorders, overview, NMDA receptors' synaptic localization and binding to PSD-MAGUK protein family play a key role in the control of downstream signals resulting from receptor activation, physiological function, overview
-
-
-
additional information
?
-
-
MAGUKs contain three PSD-95/Discs large/Zona occludens 1, i.e. PDZ, domains, an src-homology 3, i.e. SH3, domain and a C-terminal guanylate kinase domain and play a key role in the regulation of the intracellular trafficking and synaptic localization of ionotropic glutamate receptors. In particular, the postsynaptic density-95-like subfamily of MAGUKs, PSD-MAGUKs, organizes ionotropic glutamate receptors and their associated signaling proteins in the postsynaptic density of the excitatory synapse regulating the strength of synaptic activity. Alterations of PSD-MAGUK protein interaction with N-methyl-D-aspartate, NMDA, receptors regulatory subunits are common events in several CNS disorders, overview. NMDA receptors' synaptic localization and binding to PSD-MAGUK protein family play a key role in the control of downstream signals resulting from receptor activation, physiological function, overview. The enzyme plays a role in excitotoxicity and neurodegenerative disorders, e.g. in Parkinson disease and Alzheimer disease. Physiological functions, detailed overview
-
-
-
additional information
?
-
-
synaptic scaffolding molecule, S-SCAM, is a synaptic protein, which harbors five or six PSD-95/Discs large/ZO-1, a guanylate kinase, and two WW domains. S-SCAM is associated with beta-DG and neuroligin 2 at inhibitory synapses, and functions as a linker between the dystrophin glycoprotein complex and the neurexin-neuroligin complex, complex formation analysis, overview
-
-
-
additional information
?
-
-
the cytosolic isozyme is indispensable for the growth and development of plants, but not for chloroplast development, while the plastid/mitochondrial isozyme is is essential for chloroplast differentiation, overview
-
-
-
additional information
?
-
-
the post-synaptic density-95 membrane associated guanylate kinase family of scaffolding proteins, MAGUK, associate with N-methyl-D-aspartate receptor NR2 subunits via their C-terminal glutamate serine, or aspartate/glutamate, valine motifs. N-methyl-D-aspartate receptors are a subclass of ionotropic glutamate receptors that are trafficked and/or clustered at synapses by MAGUK. Receptor binding of PSD variants differin the impact on the stabilisation, turnover and compartmentalisation of N-methyl-D-aspartate receptor subtypes in neurones during development and in the mature brain
-
-
-
additional information
?
-
Q8VGC3
the voltage-gated calcium channel beta1b contains a conserved guanylate kinase domain, which is alone recapitulating calcium channel beta-subunit CaVbeta-mediated modulation of channel activation facilitating inactivation of the voltage-gated channel. CaVbeta can switch the inactivation phenotype conferred to CaV2.3 from slow to fast after posttranslational modifications during channel biogenesis, modulation mechanism, overview, the voltage-gated calcium channel beta2a contains a conserved guanylate kinase domain, which is alone recapitulating calcium channel beta-subunit CaVbeta-mediated modulation of channel activation inhibiting inactivation of the voltage-gated channel. CaVbeta can switch the inactivation phenotype conferred to CaV2.3 from slow to fast after posttranslational modifications during channel biogenesis, modulation mechanism, overview
-
-
-
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Ca2+
-
no activator
Ca2+
-
10% as effective as Mg2+
Ca2+
-
activation
Ca2+
-
activation
Co2+
-
can partially replace Mg2+
Co2+
-
less than 7% as effective as Mg2+
Co2+
-
activation
Co2+
-
can partially replace Mg2+
Co2+
-
can partially replace Mg2+
Fe2+
-
activation, 90% as effective as Mg2+
Fe2+
-
no activator
Fe2+
-
activation, 90% as effective as Mg2+
Fe3+
-
activation, less than 7% as effective as Mg2+
Fe3+
-
no activator
K+
-
activation; activity of dGMP kinase progressively enhanced as the concentration of KCl is increased to 250 mM, GMP phosphorylation unaffected; dGMP, not GMP as substrate
K+
-
activation; dGMP, not GMP as substrate
K+
-
activation; dGMP, not GMP as substrate
K+
-
activation
Li+
-
partial activity
Mg2+
-
-
Mg2+
-
requirement
Mg2+
-
requirement
Mg2+
-
active substrate: MgATP2-; requirement
Mg2+
-
active substrate: MgATP2-; requirement
Mg2+
Q92GC9, -
-
Mn2+
-
equally effective as Mg2+; requirement
Mn2+
-
requirement
Mn2+
-
60% as effective as Mg2+; equally effective as Mg2+; requirement
Mn2+
-
requirement
Mn2+
-
requirement
Mn2+
-
requirement
Mn2+
-
requirement
Na+
-
activation
Na+
-
no activator
Na+
-
activation
NH4+
-
activation; less effective than K+
NH4+
-
activation; less effective than K+
NH4+
-
activation
Ni2+
-
activation
Rb+
-
activation, less effective than K+
Zn2+
-
activation; can partially replace Mg2+
Zn2+
-
less than 7% as effective as Mg2+
Zn2+
-
activation
Mn2+
-
requirement
additional information
-
GMP-kinase activity is less sensitive to metal ions than dGMP-kinase activity
additional information
-
-
additional information
-
-
additional information
-
no activation by Sr2+ or Cs2+
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
5,5'-dithiobis(2-nitrobenzoate)
-
-
5,5'-dithiobis(2-nitrobenzoate)
-
-
6-Selenoguanosine 5'-phosphate
-
GMP-phosphorylation, pI 4.9-isozyme, competitive with respect to GMP
6-Thioguanosine 5'-phosphate
-
dGMP-phosphorylation; not thiodeoxyguanosine derivative
6-Thioguanosine 5'-phosphate
-
GMP-phosphorylation, pI 4.9-isozyme, competitive with respect to GMP
8-azaguanosine 5'-monophosphate
-
(d)GMP-phosphorylation
8-Bromoguanosine 5'-monophosphate
-
(d)GMP-phosphorylation
9-(1,3-dihydroxy-2-propylmethyl)guanine 5'-monophosphate
-
-
9-(2-hydroxyethoxymethyl)guanine 5'-monophosphate
-
-
9-(6,6-difluoro-6-phosphonohexyl)guanine
-
competitive with respect to GMP, non-competitive with respect to ATP
-
9-(6-phosphonohexyl)guanine
-
competitive with respect to GMP, non-competitive with respect to ATP
-
AMP
-
10-15% inhibition at 5 mM
Ap5G
P60546
Ap5G locks an incompletely closed conformation of the enzyme, in which the adenine moiety is located outside its expected binding site. Instead, it binds at a subunit interface that is unique to the bacterial enzyme, which is in equilibrium between a dimeric and an hexameric form in solution.
ATP
-
free form, substrate inhibition, competitive toward MgATP2-
Ca2+
-
in the presence of Mg2+
CMP
-
10-15% inhibition at 5 mM
dAMP
-
10-15% inhibition at 5 mM
dCMP
-
10-15% inhibition at 5 mM
dGMP
-
competitive inhibitor to GMP
dGMP
-
competitive versus GMP and mixed-type versus ATP
EDTA
-
85% inhibition at 3 mM
GDP
-
GMP-phosphorylation
GMP
-
competitive inhibitor to dGMP
GMP
-
non competitive with respect to MgATP2- because of the formation of an abortive complex guanylate kinase-MgATP2-GMP
GTP
-
GMP-phosphorylation
indol-3-acetic acid
-
GMP + ATP protect
N-ethylmaleimide
-
-
N-ethylmaleimide
-
-
p-chloromercuribenzoic acid
-
1,4-dithiothreitol reverses
p-hydroxymercuribenzoate
-
no effect at 0.25 mM, 30% activity at 2.5 mM
p-hydroxymercuribenzoate
-
-
p-hydroxymercuribenzoate
-
-
UMP
-
10-15% inhibition at 5 mM
additional information
-
GMP-phosphorylation is less sensitive to metal ions than dGMP-phosphorylation; minimal inactivation by iodoacetate and iodoacetamide not affected by the presence or absence of KCl; no inhibition by 2-mercaptoethanol, 1,4-dithiothreitol
-
additional information
-
no inhibition by 2-mercaptoethanol, 1,4-dithiothreitol; no inhibition by guanosine, AMP, CMP, UMP, XMP, 6-thioinosine 5'-phosphate
-
additional information
-
guanylic nucleotides strongly inhibit, compete with GMP
-
additional information
-
no inhibition by 9-(5-phosphonopentyl)guanine (i.e. isosteric analogue of acyclovir 5'-monophosphate)
-
additional information
-
no inhibition by TMP and by 2-mercaptoethanol up to 5 mM
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
additional information
-
no activation by EDTA
-
additional information
-
no activation by 1,4-dithiothreitol or 2-mercaptoethanol
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.052
-
(R)-ganciclovir phosphonate
-
pH 7.5, 37C
2.1
-
6-thioguanosine 5'-monophosphate
-
pH 7.5, 30C
0.013
-
8-azaguanosine 5'-monophosphate
-
pH 7.5, 30C
0.07
-
8-azaguanosine 5'-monophosphate
-
pH 7.5, 30C
0.091
-
8-azaguanosine 5'-monophosphate
-
pH 7.5, 30C
0.25
-
9-(5-phosphonopentyl)guanine
-
pH 7.5, 30C
23.6
-
Adenosine triphosphate
Q92GC9, -
-
0.12
-
ATP
-
pH 7.5, 30C
0.18
-
ATP
-
pH 7.5, 30C
0.19
-
ATP
-
pH 7.5, 30C
0.43
-
ATP
-
-
1
-
ATP
-
pH 8.0, 37C, dGMP kinase activity
1.25
-
Co2+
-
-
0.01
-
dGMP
-
pH 7.5, 30C
0.028
-
dGMP
-
pH 7.5, 30C
0.03
-
dGMP
-
pH 7.5, 37C
0.072
-
dGMP
-
pH 8.0, 37C
0.0731
-
dGMP
-
mutant Y76F
0.074
-
dGMP
-
pH 7.5, 30C
0.0746
-
dGMP
-
wild-type enzyme
0.083
-
dGMP
-
pH 7.5, 30C
0.1816
-
dGMP
-
mutant D74A
0.1894
-
dGMP
-
mutant E101D
0.2364
-
dGMP
-
mutant N103D
0.3
-
dGMP
-
pH 8.0, 37C, NH4+ as activator ion
0.38
-
dGMP
-
pH 7.5, 25C
0.4
-
dGMP
-
-
0.047
-
ganciclovir monophosphate
-
pH 7.5, 37C
0.045
0.054
ganciclovir-MP
-
-
0.097
-
GDP
-
pH 7.5, 25C
0.002
-
GMP
-
mutant S35P
0.0025
-
GMP
-
mutant S35P/D101S
0.006
-
GMP
-
pH 7.5, 30C
0.01
-
GMP
-
pH 7.5, 30C
0.013
-
GMP
-
-
0.015
-
GMP
-
wild type enzyme, in 100 mM TrisHCl buffer pH 7.5, 4 mM ATP, 10 mM MgCl2, 1 mM dithiothreitol, 100 mM KCl, at 30C
0.018
-
GMP
-
pH 7.5, 30C
0.0222
-
GMP
-
wild-type enzyme
0.025
-
GMP
Q64520
pH 8.0, 37C
0.025
-
GMP
-
-
0.026
-
GMP
-
pH 7.5, 37C
0.032
-
GMP
-
pH 7.5, 30C
0.041
-
GMP
-
wildtype
0.0592
-
GMP
-
mutant Y76F
0.0616
-
GMP
-
mutant E101D
0.08
-
GMP
-
-
0.091
-
GMP
-
pH 7.5, 25C
0.091
-
GMP
-
pH 7.7, 25C
0.1933
-
GMP
-
mutant D74A
0.2265
-
GMP
-
mutant N103D
0.26
-
GMP
-
pH 8.0, 37C
0.27
-
GMP
-
mutant S35N/V168F, in 100 mM TrisHCl buffer pH 7.5, 4 mM ATP, 10 mM MgCl2, 1 mM dithiothreitol, 100 mM KCl, at 30C
0.5
-
GMP
-
pH 7.5, 25C, S80A mutant
1.8
-
GMP
-
pH 7.7, 25C, Y78F mutant
0.0051
-
guanosine monophosphate
Q92GC9, -
-
10.8
347
K+
-
-
0.017
-
MgADP2-
-
pH 7.5, 25C
-
0.2
-
MgATP2-
-
pH 7.5, 25C
0.2
-
MgATP2-
-
pH 7.7, 25C
0.23
-
MgATP2-
-
pH 7.5, 25C, S80A mutant
0.42
-
MgATP2-
-
-
0.45
-
MgATP2-
-
pH 7.7, 25C, Y78F mutant
0.75
-
Mn2+
-
-
additional information
-
additional information
-
kinetic parameters of several substrates for 4 isoenzymes
-
additional information
-
additional information
-, P0A5I4
detailed reaction kinetics, overview
-
additional information
-
additional information
-
kinetics of wild-type and mutant enzymes
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
90
-
ATP
-
pH 7.7, 25C, reverse reaction
2
8
dGMP
-
mutant Y76F
26.5
-
dGMP
-
mutant E101D
26.8
-
dGMP
-
mutant N103D
33.1
-
dGMP
-
mutant D74A
43
-
dGMP
-
wild-type enzyme
51
-
dGMP
-
pH 7.5, 25C
394
-
GMP
-
pH 7.7, 25C, forward reaction
848
-
GMP
-
mutant E101D
946
-
GMP
-
wild-type enzyme
1032
-
GMP
-
mutant Y76F
1080
-
GMP
-
mutant N103D
1121
-
GMP
-
mutant D74A
130
-
GTP
-
calculated as GDP produced
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.043
-
9-(1,3-dihydroxy-2-propylmethyl)guanine 5'-monophosphate
-
pH 7.5, isoenzyme 4
0.052
-
9-(1,3-dihydroxy-2-propylmethyl)guanine 5'-monophosphate
-
pH 7.5, isoenzyme 4
0.06
-
9-(1,3-dihydroxy-2-propylmethyl)guanine 5'-monophosphate
-
pH 7.5, isoenzyme 1
0.067
-
9-(1,3-dihydroxy-2-propylmethyl)guanine 5'-monophosphate
-
pH 7.5, isoenzyme 2
0.45
-
9-(2-hydroxyethoxymethyl)guanine 5'-monophosphate
-
pH 7.5, isoenzyme 4
0.65
-
9-(2-hydroxyethoxymethyl)guanine 5'-monophosphate
-
pH 7.5, isoenzyme 2
0.67
-
9-(2-hydroxyethoxymethyl)guanine 5'-monophosphate
-
pH 7.5, isoenzyme 3
0.84
-
9-(2-hydroxyethoxymethyl)guanine 5'-monophosphate
-
pH 7.5, isoenzyme 1
0.14
-
9-(6,6-difluoro-6-phosphonohexyl)guanine
-
pH 7.5, 30C, higher affinity than 9-(6-phosphonohexyl)guanine for guanylate kinases al pH values below 7.5
-
0.11
-
9-(6-phosphonohexyl)guanine
-
pH 7.5, 30C
-
0.148
-
dGMP
-
versus GMP
0.4
-
dGMP
-
versus ATP
0.57
-
dGMP
-
pH 7.5
0.215
-
GDP
-
pH 7.5, 25C
0.035
-
GMP
-
pH 7.5, 25C
0.035
-
GMP
-
pH 7.7, 25C
0.064
-
GMP
-
pH 7.5
0.63
-
GMP
-
pH 7.7, 25C, Y78F mutant
0.037
-
MgADP-
-
pH 7.5, 25C
0.08
-
MgATP2-
-
pH 7.5, 25C
0.08
-
MgATP2-
-
pH 7.7, 25C
0.16
-
MgATP2-
-
pH 7.7, 25C, Y78F mutant
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0005
-
Ap5G
P60546
The crystal structure of EcGMPK in complex with Ap5G solved at 2.5 resolution.
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.0012
-
-
E72Q mutant
0.0032
-
-
D103N mutant, adenylate kinase activity
0.0057
-
-
E72Q mutant, adenylate kinase activity
0.024
-
-
E72Q/D103N mutant
0.088
-
-
D103N mutant
0.44
-
-
-
1.24
-
-
-
2.5
-
-
mutant S35P; mutant S35P/D101S
28
-
-
-
30
-
-
with substrates ATP and dGMP
323
-
-
rod outer segment
354
-
-
retina
750
-
-
with substrate ATP and GMP
999
-
Q92GC9, -
290 Vmax for adenosine triphosphate (ATP); 92 Vmax for guanosine monophosphate (GMP)
1581
-
-
wildtype
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7
10
-
dGMP-phosphorylation
7
10.9
-
GMP-phosphorylation
7
9
-
equal activity in Tris-HCl buffer and 3,3-dimethylglutarate buffer
7.3
8.2
-
Tris-chloride buffer
7.5
-
-
assay at
8
-
-
assay at
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5
10.9
-
about half-maximal activity at pH 5 and maximal activity at pH 10.9, GMP-phosphorylation, calf thymus
5.2
7.5
-
about half-maximal activity at pH 5.2 and 7.5
5.7
10.9
-
about half-maximal activity at pH 5.7 and 10.9, dGMP-phosphorylation, calf thymus
6.5
9
-
70% of maximal activity at pH 6.5 and 9
6.8
8.6
-
about 80% of maximal activity at pH 6.8 and 8.6, about 95% of maximal activity at pH 7.3 and 8
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
25
-
-
assay at
30
-
-
assay at
30
-
-
assay at
37
-
-
assay at
37
-
-
assay at
37
-
-
assay at
pI VALUE
pI VALUE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
4.7
4.8
-
3 isoelectric variants, predominant form: pI 4.9, agarose gel electrophoresis and isoelectric focusing
4.7
4.8
-
3 isoelectric variants
4.9
-
-
4 isoelectric variants, agarose gel electrophoresis and isoelectric focusing
5.8
-
-
pH 7.7, 25C
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
plastid/mitochondrial isozyme
Manually annotated by BRENDA team
-
cytosolic isozyme
Manually annotated by BRENDA team
-
post-synaptic density-95 membrane associated, association with N-methyl-D-aspartate receptor NR2 subunits via their C-terminal glutamate serine, aspartate/glutamate, valine motifs
Manually annotated by BRENDA team
-
plastid/mitochondrial isozyme
Manually annotated by BRENDA team
Escherichia coli JE24F+
-
-
-
-
Manually annotated by BRENDA team
-
S-SCAM is associated with beta-dystroglycan and neuroligin 2 at inhibitory synapses, and functions as a linker between the dystrophin glycoprotein complex and the neurexin-neuroligin complex, complex formation analysis, overview
Manually annotated by BRENDA team
-
; post-synaptic density-95 membrane associated
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Anaplasma phagocytophilum (strain HZ)
Coxiella burnetii (strain RSA 493 / Nine Mile phase I)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Listeria monocytogenes serovar 1/2a (strain ATCC BAA-679 / EGD-e)
Plasmodium falciparum (isolate 3D7)
Plasmodium vivax (strain Salvador I)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Staphylococcus aureus (strain COL)
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
20000
-
-
gel filtration
20000
-
-
gel filtration
20000
-
-
dynamic light scattering and gel filtration
20500
-
-
gel filtration
21700
-
-
deduced from the amino acid composition
21900
-
Q64520
deduced from the amino acid composition
22000
-
-
calculated
22010
-
Q16774
deduced from the amino acid composition and detected by mass spectrometry, adducts with sulfate and not phosphate are detected in mass spectrometry
23460
-
P60546
monomer, electrospray ionization-mass spectrometry
24000
-
-
guanylate monophosphate kinase
25000
-
-
gel filtration
72000
-
-
gel filtration
88000
-
-
equilibrium centrifugation
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 22000, SDS-PAGE
dimer
-
One of the two SaGMK dimers within the crystal asymmetric unit has two monomers in different conformations: an open form with a bound sulfate ion (mimicking the beta-phosphate of ATP) and a closed form with bound GMP and sulfate ion. Each monomer is bound through its P-loop to a sulfate ion.
dimer
Q8VGC3
the recombinant refolded CaVbeta2a-GK is essentially a dimer
hexamer
P60546
crystallography
hexamer
P60546
X-ray diffraction data for EcGMPK in complex with GCV-MP were collected at 100 K from a single crystal on beamline ID23-1 (lambda = 0.980 A) at the European Synchrotron Radiation Facility (Grenoble, France), and is indexed and scaled using XDS and XSCALE to a resolution of 3.16 A. Crystals of EcGMPK GCV-MP belong to space group P41212 and are isomorphous to those of apo-EcGMPK, with 6 molecules related by D3 symmetry in the asymmetric unit. Each monomer was first divided in 3 domains corresponding to the LID, CORE and GMP-binding domains (except for subunit F whose GMP-binding domain is not visible in apo-EcGMPK), which were submitted to rigid body refinement.
monomer
-
1 * 23000, SDS-PAGE
monomer
-
1 * 20548, calculated from amino acid sequence
oligomer
P60546
x * 23462, thermodynamic analysis, the enzyme is in equilibrium between a dimer and higher order oligomers, whose relative amounts depend on protein concentration, ionic strength, and the presence of ATP
monomer or dimer
Q8VGC3
the recombinant and refolded CaVbeta1b-GK is a mixture of dimers and monomers
additional information
P60546
GMPKs share a highly conserved structure comprising a GMP-binding domain, a central CORE domain that carries the ATP beta-phosphate binding loop (P-loop) and a LID domain which binds the adenine base of ATP and provides catalytic residues to the phosphoryl transfer reaction.
additional information
-
synaptic scaffolding molecule, S-SCAM, is a synaptic protein, which harbors five or six PSD-95/Discs large/ZO-1, a guanylate kinase, and two WW domains
additional information
-
structural model of microtubule-associated protein-1a. Domain organization of neuronal MAGUKs, overview
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
phosphoprotein
-
PSD-MAGUK's major phosphorylation sites, regulation by phosphorylation through Ser/Thr protein kinases and also Tyr-dependent kinases, overview
phosphoprotein
-
PSD-MAGUK's major phosphorylation sites, regulation by phosphorylation, through Ser/Thr protein kinases and also Tyr-dependent kinases, overview
phosphoprotein
-
PSD-MAGUK's major phosphorylation sites, regulation by phosphorylation, through Ser/Thr protein kinases and also Tyr-dependent kinases, overview
additional information
-, P0A5I4
As is evident from the structure, GK has a clamp-like cavity, where the two lobes of the protein close through an ca. 1-nm conformational change upon binding the substrates, most of the conformational motion is induced by GMP binding. The substrates GMP and ATP drive this conformational change through several direct and indirect (via water molecules) interactions that bring the LID and nucleotide-monophosphate-binding domain (herein referred to as NMP-BD) nearer and jointly toward the CORE region, the structure closing in a vise-like motion. In this configuration, the CORE is catalytically active toward phosphoryl transfer, which relies on a residue sequence (the P-loop) that is conserved in kinases.
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
vapour diffusion method
P60546
SAP97 SH3-guanylate kinase/p-LGN18 complex, hanging drop vapor diffusion method, using 0.2M ammonium nitrate, 20% (w/v) polyethylene glycol 3350
-
crystal structure of a complex with ADP and GMP
-
SAP97 SH3-guanylate kinase/p-LGN18 complex, hanging drop vapor diffusion method, using 0.2M ammonium nitrate, 20% (w/v) polyethylene glycol 3350
Q62696
crystal structure of a complex with GMP
-
crystal structure of the enzyme with a non-acetylated N terminus in its unligated form as well as in complex with GMP
P15454
octahedral bipyramids, preliminary X-ray analysis
-
temperature-dependent space-group transitions between orthorhombic and tetragonal forms
-
Crystals grown in 20% PEG 3350, 0.2 M LiSO4 and 0.1 M Tris-HCl pH 8.
-
pH STABILITY
pH STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
4
9
-
4C, inactivation within 48 h outside this range
5.5
8.5
-
at least 15 min stable at 30C
7.5
-
-
most stable at
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
30
-
-
at least 15 min stable from pH 5.5-8.5
45
-
-
t1/2: 10 min
50
-
-
10 min, inactivation
60
-
-
10 min, 90% loss of activity
80
-
-
incubation for 2 min, 5 min, 10 min or 20 min leads to 43%, 67%, 89% or 97% loss of activity, respectively, 30 min: inactivation
100
-
-
10 min, about 80% loss of activity, t1/2: 3 min (dGMP-phosphorylation), t1/2: 4 min (GMP-phosphorylation)
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
dialysis against water, pH 6 with several changes of outer fluid inactivates, stable to dialysis for less than 36 h without changing the outer fluid
-
dilution inactivates calf thymus enzyme, KCl protects, not bovine serum albumin
-
KCl does not prevent heat inactivation
-
unstable in dilute solutions, below 0.005 mg/ml, bovine serum albumin or other suitable proteins protect, highly purified enzyme is stabilized by the presence of lactic dehydrogenase and pyruvate kinase
-
bovine serum albumin stabilizes during purification
-
2-mercaptoethanol does not stabilize
-
freeze-thawing rapidly inactivates
-
20% glycerol stabilizes: 90% original activity retained
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
4C, calf thymus enzyme, stable in the absence of thiols
-
4C, diluted calf thymus enzyme solution, 0.002 mg/ml, inactivation within 10 days, KCl protects
-
4C, partially purified calf thymus enzyme preparation in the presence of 1 M KCl, 3 months
-
-10C, more than a month
-
-20C, stable at all stages of purification
-
-20C, stable for several months after purification by Blue Sepharose and gel filtration
P60546
-25C, stable
-
0C, below, in 70% saturated ammonium sulfate, several years
-
-15C, more than 6 months
-
0-4C, 6-10 weeks
-
0C, below, in 70% saturated ammonium sulfate, several years
-
-30C, in N-ethylmorpholine-HCl buffer, pH 7.5, several years
-
4C, at pH-values below 4 or above 9, inactivation within 48 h
-
4C, in 20% glycerol, at least 1 month
-
4C, in N-ethylmorpholine-HCl buffer, pH 7.5, several years
-
glycerol, 20%, stabilizes labile enzyme during storage
-
0C, below, in 70% saturated ammonium sulfate, several years
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
method that includes DEAE-cellulose, hydroxyapatite and Sephadex G-100 chromatography
-
method that includes Sephadex and two DEAE-cellulose chromatography
-
recombinant ecGMPK is purified by a two-step chromatography procedure involving affinity chromatography on Blue Sepharose and gel filtration
P60546
method that includes DEAE-Sephacel and Blue Sepharose CL 6B chromatography
-
4 isoenzymes purified by a method that includes GMP agarose chromatography and isoelectric focusing
-
method
-
method that includes DEAE-cellulose, Sephadex-75 chromatography and isoelectric focusing
-
Ni2+-NTA agarose affinity column chromatography and gel filtration
-
method
Q64520
partial by a method that includes DEAE-cellulose chromatography
-
TALON metal affinity resin column chromatography
-
method that includes DEAE-cellulose and Sephadex-75 chromatography
-
Ni2+-NTA agarose affinity column chromatography
Q62696
partial by a method that includes DEAE-cellulose, hydroxyapatite and Sephadex G-200 chromatography
-
recombinant His6-tagged PSD-95 SH3-GK from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, recombinant GST-tagged PSD-95 SH3-GK from Escherichia coli strain BL21(DE3) by glutathione affinity chromatography
-
recombinant protein
-
method that includes DEAE-cellulose, hydroxyapatite and Sephadex-75 chromatography
-
method that includes DEAE-Sephacel, Cibacron-blue Sepharose and two Sephadex-75 chromatography
-
recombinant protein
-
method that includes DEAE-cellulose and Sephadex-75 chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expression in Escherichia coli strain BLI5
P60546
expressed in Escherichia coli
-
expressed in Escherichia coli BL21(DE3) cells
-
transient expression in HEK293 cells, with N-methyl-D-aspartate receptor, wild-type and mutant, cell surface co-expression
-
expressed in Escherichia coli
-
gene Rv1389c
-, P0A5I4
DNA and amino acid sequence determination and analysis, sequence comparison
-
expressed in Escherichia coli JM109 cells
-
expressed in Escherichia coli BL21(DE3) cells
Q62696
expression of fluorescence-tagged S-SCAM in COS-7 cells
-
expression of GFP-tagged enzyme in COS cells, expression of His6-tagged and GST-tagged PSD-95 SH3-GK in Escherichia coli strain BL21(DE3)
-
overexpression of Cavbeta1b in Xenopus laevis oocytes in inclusion bodies; overexpression of Cavbeta2a in Xenopus laevis oocytes in inclusion bodies
Q8VGC3
PSD-95, containing SH3GK residues 417-724 and CASK, containing SH3GK residues 591-909, expression in Escherichia coli
-
expressed in Escherichia coli
-
expression in Escherichia coli
-
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
there is an approximately 40% drop in guanylate kinase mRNA expression in cell lines resistant to 9-[2-(phosphonomethoxyethyl)guanine] and 9-[2-(phosphonomethoxyethyl)diaminopurine]
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
C3S/C5S
-
PSD-95aC3S/C5S mutant
S35N/V168F
-
the mutations significantly suppress enzyme catalytic activity
D103N
-
active
E72Q
-
no guanylate or adenylate kinase activity
D74A
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
E101D
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
N103D
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
P564S/S631D
-
PSD-95 construct
S35P
-
reduced activity
S35P/D101S
-
reduced activity
S80A
-
sluggish enzyme
Y78F
-
affinity for MgATP2- similar to wild type but affinity for GMP decreases by a factor of 12
E72Q/D103D
-
no active
additional information
-
RNAi knockdown of the cytosolic enzyme, a v2 mutant is temperature-sensitive and develops chlorotic leaves at restrictive temperatures, the v2 mutation causes inhibition of chloroplast differentiation; in particular, it disrupts the chloroplast translation machinery during early leaf development
Y76F
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
additional information
-
construction of mutant PSD-95 SH3-GK which contains a deleterious point mutation in the C-terminal SH3 domain
Renatured/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
complete denaturation of the protein is not reversible due to aggregation at the unfolded state
P60546
recombinant Cavbeta1b after overexpression in inclusion bodies in Xenopus laevis oocytes; recombinant Cavbeta2a from inclusion bodies after overexpression in Xenopus laevis oocytes
Q8VGC3
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
drug development
-
the guanylate-kinase-deficient Escherichia coli strain relies on the presence of a plasmid-borne, functional guanylate kinase for viability. Such a strain will be beneficial to assess the role of specific amino acids of guanylate kinase in structure, function, drug activation, and drug resistance
medicine
P60546
GMPK from bacterial pathogens, in which this enzyme is essential, are potential targets for therapeutic inhibition.
drug development
Escherichia coli TS202A
-
the guanylate-kinase-deficient Escherichia coli strain relies on the presence of a plasmid-borne, functional guanylate kinase for viability. Such a strain will be beneficial to assess the role of specific amino acids of guanylate kinase in structure, function, drug activation, and drug resistance
-