Information on EC 2.7.4.3 - adenylate kinase and Organism(s) Escherichia coli and UniProt Accession P69441

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This record set is specific for:
Escherichia coli
UNIPROT: P69441


The taxonomic range for the selected organisms is: Escherichia coli

The enzyme appears in selected viruses and cellular organisms

EC NUMBER
COMMENTARY hide
2.7.4.3
-
RECOMMENDED NAME
GeneOntology No.
adenylate kinase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + AMP = 2 ADP
show the reaction diagram
ATP + AMP = 2 ADP
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho group transfer
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
adenosine ribonucleotides de novo biosynthesis
-
-
purine metabolism
-
-
Purine metabolism
-
-
Thiamine metabolism
-
-
Metabolic pathways
-
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Biosynthesis of secondary metabolites
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Biosynthesis of antibiotics
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-
SYSTEMATIC NAME
IUBMB Comments
ATP:AMP phosphotransferase
Inorganic triphosphate can also act as donor.
CAS REGISTRY NUMBER
COMMENTARY hide
9013-02-9
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
enzyme adenylate kinase dynamics-function relationships, modelling using crystal structure PDB ID 1ANK, comparisons of different enzyme structures and substrate binding structures, detailed overview
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + AMP
ADP + ADP
show the reaction diagram
ADP
AMP + ATP
show the reaction diagram
-
-
-
-
?
ADP + ADP
?
show the reaction diagram
-
facilitates storage and use of the high energy of the adenine nucleotides, involved in maintenance of equilibrium among adenine nucleotides and maintenance of energy charge, important to energy economy of living systems
-
-
r
ADP + ADP
ATP + AMP
show the reaction diagram
-
-
-
-
r
ADP + TDP
AMP + TTP
show the reaction diagram
ATP + 7-deazaadenosine 5'-monophosphate
ADP + 7-deazaadenosine 5'-diphosphate
show the reaction diagram
-
i.e. tubercidine monophosphate
-
-
?
ATP + adenine-9-beta-D-arabinofuranoside 5'-monophosphate
ADP + adenine-9-beta-D-arabinofuranoside 5'-diphosphate
show the reaction diagram
-
-
-
-
?
ATP + AMP
2 ADP
show the reaction diagram
ATP + AMP
ADP + ADP
show the reaction diagram
ATP + AMP + CDP
ADP + AMP + CTP
show the reaction diagram
-
-
-
-
r
ATP + CDP
ADP + CTP
show the reaction diagram
-
-
nucleoside triphosphate synthesis by beta-phosphoryl transfer from ADP to any bound nucleoside diphosphate
-
r
ATP + dAMP
ADP + dADP
show the reaction diagram
-
2'-dAMP or 3'-dAMP
-
-
?
GTP + AMP + CDP
GDP + AMP + CTP
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + AMP
ADP + ADP
show the reaction diagram
-
-
-
-
r
ADP + ADP
?
show the reaction diagram
-
facilitates storage and use of the high energy of the adenine nucleotides, involved in maintenance of equilibrium among adenine nucleotides and maintenance of energy charge, important to energy economy of living systems
-
-
r
ADP + TDP
AMP + TTP
show the reaction diagram
-
Escherichia coli adenylate kinase is able to synthesize TTP, but the activity is too low to explain the high rate of TTP accumulation uring amino acid starvation of cells
-
-
?
ATP + AMP
2 ADP
show the reaction diagram
-
-
-
-
r
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ba2+
-
forms complex with di- or trinucleotide
Ca2+
-
metal ion forms complex with di- or trinucleotide
Co2+
-
can replace Mg2+, Mn2+ or Ca2+ less efficiently
Mn2+
-
forms complex with di- or trinucleotide
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3'-O-(4-benzoyl)benzoyl-ATP
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-
5,5'-dithiobis(2-nitrobenzoic acid)
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-
P1,P5-di(adenosine-5') pentaphosphate
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P1,P5-di(adenosine-5')pentaphosphate
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.85
2'-dAMP
-
cosubstrate ATP, pH 7.4, 27C
0.73
7-deazaadenosine 5'-monophosphate
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cosubstrate ATP, pH 7.4, 27C
1.3 - 1.37
adenine-9-beta-D-arabinofuranoside 5'-monophosphate
-
cosubstrate ATP, pH 7.4, 27C
0.09 - 0.092
ADP3-
-
ADP, 30C
0.038 - 0.04
AMP
0.048 - 0.3
ATP
additional information
additional information
-
single molecule conformational dynamics for prediction of open and closed kinetic rates at the whole temperature ranges from 10C to 50C. Identification of key residues and contacts responsible for the conformational transitions are identified by following the time evolution of the two-dimensional spatial contact maps and characterizing the transition state as well as intermediate structure ensembles
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
129
-
mutant S129F
250
-
mutant P87S
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
27
-
assay at
30
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highly active at 30C
50
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around 50C
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
additional information
-
-
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
additional information
-
-
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
22940
-
sedimentation equilibrium
23559
-
1 * 23559, calculated from nucleotide sequence
23560
-
calculated from nucleotide sequence
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
analysis of atomically detailed conformational transition pathway of adenylate kinase in the absence and presence of an inhibitor. In the ligand-free state, there is no significant barrier separating the open and closed conformations. The enzyme samples near closed conformations, even in the absence of its substrate. The ligand binding event occurs late, toward the closed state, and transforms the free energy landscape. In the ligand-bound state, the closed conformation is energetically most favored with a large barrier to opening
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coarse grained model for the interplay between protein structure, folding and function. High strain energy is correlated with localized unfolding during the functional transition. Competing native interactions from the open and closed form can account for the large conformational transitions. Local unfolding may be due, in part, to competing intra-protein interactions
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coarse-grained models and nonlinear normal mode analysis. Intrinsic structural fluctuations dominate LID domain motion, whereas ligand-protein interactions and local unfolding are more important during NMP domain motion. LID-NMP domain interactions are indispensable for efficient catalysis. LID domain motion precedes NMP domain motion, during both opening and closing, providing mechanistic explanation for the observed 1:1:1 correspondence between LID domain closure, NMP domain closure, and substrate turnover
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single molecule conformational dynamics for prediction of open and closed kinetic rates at the whole temperature ranges from 10C to 50C. Identification of key residues and contacts responsible for the conformational transitions are identified by following the time evolution of the two-dimensional spatial contact maps and characterizing the transition state as well as intermediate structure ensembles
-
sitting drop vapor diffusion method, using 3% (w/v) PEG 2K with 1.8-2.3 M ammonium sulfate, pH 7.0-7.3
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solution-state NMR approach to probe the native energy landscape of adenylate kinase in its free form, in complex with its natural substrates, and in the presence of a tight binding inhibitor. Binding of ATP induces a dynamic equilibrium in which the ATP binding motif populates both the open and the closed conformations with almost equal populations. A similar scenario is observed for AMP binding, which induces an equilibrium between open and closed conformations of the AMP binding motif. Simultaneous binding of AMP and ATP is required to force both substrate binding motifs to close cooperatively. Unidirectional energetic coupling between the ATP and AMP binding sites
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atomistic molecular dynamics simulation of the complete conformational transition. Starting from the closed conformation, half-opening of the AMP-binding domain precedes a partially correlated opening of the LID and AMP-binding domain, defining the second phase. A highly stable salt bridge D118-K136 at the LID-CORE interface, contributing substantially to the total nonbonded LID-CORE interactions, is a major factor that stabilizes the open conformation
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characterization of both ATP and AMP conformations, conformations of ATP, AMP, and the ATP analogue adenylyl imidodiphosphate
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dynamics sampling simulations of the domain conformations of unliganded adenylate kinase. There is a bias towards the open-domain conformation for both domain pairs but no appreciable barrier. The interaction with the substrate enables the enzyme to adopt the closed-domain conformation. For the ATP-core domain pair, this interaction comes from a cation-pi interaction between Arg119 and the adenine moiety of ATP. For the AMP-core domain pair it is between Thr31 and the adenine moiety of AMP
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in complex with inhibitor P1,P5-di(adenosine-5)-pentaphosphate that simulates well the binding of substrates ATP and AMP. The alpha-phosphate of AMP is well positioned for a nucleophilic attack on the gamma-phosphate of ATP, giving a stabilized pentacoordinated transition state with nucleophile and leaving group in the apical positions of a trigonal bipyramide
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x-ray diffraction analysis
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
52
-
the melting temperature of the free enzyme is at 52C
additional information
-
thermostability of mutant enzymes
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
remarkably stable in dilute solution in the absence of any protective agent
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-10C, partially purified, more than 1 month
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Affi-Gel Blue Gel column chromatography, Q-Sepharose column chromatography, and S-200 gel filtration
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ammonium sulfate fractionation and Q-Sepharose column chromatography
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single-step purification procedure from overproducing strain GT836
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
overexpression in Escherichia coli
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wild-type and thermosensitive mutants
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
F137W
-
mutation in domain that closes over the ATP binding site
F86W
-
mutation in AMP binding site
P87S
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thermosensitive enzyme, about 50% of wild type activity
S129F
-
about 25% of wild type activity
S41W
-
mutation in domain that closes over the AMP binding site
Y133W
-
mutation in domain that closes over the ATP binding site
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
-
coarse grained model for the interplay between protein structure, folding and function which is applicable to allosteric or non-allosteric proteins. High strain energy is correlated with localized unfolding during the functional transition. Competing native interactions from the open and closed form can account for the large conformational transitions. Local unfolding may be due, in part, to competing intra-protein interactions