Information on EC 3.6.4.12 - DNA helicase

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
3.6.4.12
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RECOMMENDED NAME
GeneOntology No.
DNA helicase
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + H2O = ADP + phosphate
show the reaction diagram
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SYSTEMATIC NAME
IUBMB Comments
ATP phosphohydrolase (DNA helix unwinding)
DNA helicases utilize the energy from ATP hydrolysis to unwind double-stranded DNA. Some of them unwind duplex DNA with a 3' to 5' polarity [1,3,5,8], others show 5' to 3' polarity [10,11,12,13] or unwind DNA in both directions [14,15]. Some helicases unwind DNA as well as RNA [9,10]. May be identical with EC 3.6.4.13 (RNA helicase).
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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UniProt
Manually annotated by BRENDA team
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UniProt
Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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SwissProt
Manually annotated by BRENDA team
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Manually annotated by BRENDA team
replicase polyprotein 1ab
SwissProt
Manually annotated by BRENDA team
Methanothermobacter thermautotrophicum
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Manually annotated by BRENDA team
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UniProt
Manually annotated by BRENDA team
gene 80
UniProt
Manually annotated by BRENDA team
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SwissProt
Manually annotated by BRENDA team
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SwissProt
Manually annotated by BRENDA team
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SwissProt
Manually annotated by BRENDA team
strain R6
UniProt
Manually annotated by BRENDA team
wild-type and mutant strains E233Sh (E233S double-crossover transformant generated with pMIDherA via herA downstream insertion, harboring the Tg arm pyrEF lacS Out-arm::In-arm), and mutant strain E233SherA (E233S with herA, herA on the complementing plasmid pSSR)
UniProt
Manually annotated by BRENDA team
wild-type and mutant strains E233Sh (E233S double-crossover transformant generated with pMIDherA via herA downstream insertion, harboring the Tg arm pyrEF lacS Out-arm::In-arm), and mutant strain E233SherA (E233S with herA, herA on the complementing plasmid pSSR)
UniProt
Manually annotated by BRENDA team
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SwissProt
Manually annotated by BRENDA team
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UniProt
Manually annotated by BRENDA team
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UniProt
Manually annotated by BRENDA team
WNV
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Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
malfunction
physiological function
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2'(3')-O-(N-methylanthraniloyl)ATP + H2O
2'(3')-O-(N-methylanthraniloyl)ADP + phosphate
show the reaction diagram
the fluorescent ATP analogue is used throughout all experiments to provide a complete ATPase cycle for a single nucleotide species
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?
2',3'-ATP + H2O
2',3'-ADP + phosphate
show the reaction diagram
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274% of the ability to support helicase catalyzed DNA unwinding compared to ATP
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?
2',3'-ddATP + H2O
2',3'-ddADP + phosphate
show the reaction diagram
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274% relative ability to support DNA unwinding by nonstructural protein 3, reported as percentage relative to ATP
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?
2'-amino-ATP + H2O
2'-amino-ADP + phosphate
show the reaction diagram
2'-ara-ATP + H2O
2'-ara-ADP + phosphate
show the reaction diagram
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102% of the ability to support helicase catalyzed DNA unwinding compared to ATP
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?
2'-azido-ATP + H2O
2'-azido-ADP + phosphate
show the reaction diagram
2'-dATP + H2O
2'-dADP + phosphate
show the reaction diagram
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157% relative ability to support DNA unwinding by nonstructural protein 3, reported as percentage relative to ATP
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?
2'-fluoro-ATP + H2O
2'-fluoro-ADP + phosphate
show the reaction diagram
2'-O-methyl-ATP + H2O
2'-O-methyl-ADP + phosphate
show the reaction diagram
2-amino-ATP + H2O
2-amino-ADP + phosphate
show the reaction diagram
3'-dATP + H2O
3'-dADP + phosphate
show the reaction diagram
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307% relative ability to support DNA unwinding by nonstructural protein 3, reported as percentage relative to ATP
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?
ATP + H2O
ADP + phosphate
show the reaction diagram
CTP + H2O
CDP + phosphate
show the reaction diagram
dATP + H2O
ADP + phosphate
show the reaction diagram
dATP + H2O
dADP + phosphate
show the reaction diagram
dCTP + H2O
dCDP + phosphate
show the reaction diagram
dCTP + H2O
dCTP + phosphate
show the reaction diagram
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the enzyme translocates in a 5'-to-3' direction with respect to the substrate strand to which it is bound. The enzyme favours adenosine nucleotides (ATP and dATP) as its energy source, but utilizes to limited extents GTP, CTP, dGTP and dCTP. ATP and dATP support unwinding activity with equal efficiency. GTP, dGTP, CTP, dCTP support unwinding activity to limited extents (5-12% of that with ATP at 1.5 mM). The ATPase activity of DNA helicase II increases proportionally with increasing lengths of single-stranded DNA cofactor. In the presence of circular DNA, ATP hydrolysis continues to increase up to the longest time tested (3 h), whereas it ceases to increase after 5-10 min in the presence of shorter oligonucleotides. The initial rate of ATP hydrolysis during the first 5 min of incubation time is not affected by DNA species used. The enzyme does not dissociate from the single-stranded DNA once it is bound and is therefore highly processive
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?
dGTP + H2O
dGDP + phosphate
show the reaction diagram
dNTP + H2O
dNDP + phosphate
show the reaction diagram
dTTP + H2O
dTDP + phosphate
show the reaction diagram
dTTP + H2O
TDP + phosphate
show the reaction diagram
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helicase-catalyzed DNA unwinding by nonstructural protein 3 analyzed by molecular beacon-based helicase assay (MBHA), NTP binding occurs with similar affinities, dNTPs support faster DNA unwinding, dTTP supporting faster rates than any other canonical dNTP
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?
dUTP + H2O
dUDP + phosphate
show the reaction diagram
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?
GTP + H2O
GDP + phosphate
show the reaction diagram
N1-methyl-ATP + H2O
N1-methyl-ADP + phosphate
show the reaction diagram
N6-methyl-ATP + H2O
N6-methyl-ADP + phosphate
show the reaction diagram
NTP + H2O
NDP + phosphate
show the reaction diagram
TTP + H2O
TDP + phosphate
show the reaction diagram
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ability of various NTPs to support HCV helicase-catalyzed DNA unwinding by nonstructural protein 3 using a molecular-beacon-based helicase assay
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?
UTP + H2O
UDP + phosphate
show the reaction diagram
xanthosine 5'-triphosphate + H2O
xanthosine 5'-diphosphate + phosphate
show the reaction diagram
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7% relative ability to support DNA unwinding by nonstructural protein 3, reported as percentage relative to ATP
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?
XTP + H2O
XDP + phosphate
show the reaction diagram
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7% of the ability to support helicase catalyzed DNA unwinding compared to ATP
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?
additional information
?
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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 + H2O
ADP + phosphate
show the reaction diagram
dNTP + H2O
dNDP + phosphate
show the reaction diagram
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dNTPs support faster DNA unwinding mediated by nonstructural protein 3
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?
NTP + H2O
NDP + phosphate
show the reaction diagram
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different NTP binding rate and processivity, DNA unwinding of nonstructural protein 3
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?
additional information
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4Fe-4S cluster
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the enzyme contains a 4Fe-4S cluster
H2O2
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the iron-sulfur cluster in the N-terminus of the enzyme, RtelN, residues 1-312, is sensitive to hydrogen peroxide and nitric oxide, indicating that reactive oxygen/nitrogen species may modulate the DNA helicase activity of Rtel1 via modification of its iron-sulfur cluster but not significantly affect the DNA binding activity of RtelN
Iron-sulfur cluster
; is essential for the helicase activity
K+
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activation at 100-300 mM, inhibition above 500 mM
MgCl2
required, optimal concentration: 5 mM
MgUTP
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MgUTP stabilizes hexamers over higher oligomers
Na+
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activation at 100-300 mM, inhibition above 500 mM
nitric oxide
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the iron-sulfur cluster in the N-terminus of the enzyme, RtelN, residues 1-312, is sensitive to hydrogen peroxide and nitric oxide, indicating that reactive oxygen/nitrogen species may modulate the DNA helicase activity of Rtel1 via modification of its iron-sulfur cluster but not significantly affect the DNA binding activity of RtelN
additional information
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(2Z)-4-[2-(benzyloxy)phenyl]-2-hydroxy-4-oxobut-2-enoic acid
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low inhibitory activities
(2Z)-4-[2-[(4-chlorobenzyl)oxy]phenyl]-2-hydroxy-4-oxobut-2-enoic acid
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no or marginal inhibition activities towards ATPase activity or duplex DNA-unwinding activity
(2Z)-4-[3-(benzylamino)phenyl]-2-hydroxy-4-oxobut-2-enoic acid
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inhibition of duplex DNA-unwinding activity
(2Z)-4-[3-(benzyloxy)phenyl]-2-hydroxy-4-oxobut-2-enoic acid
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low inhibitory activities
(2Z)-4-[3-[(4-chlorobenzyl)amino]phenyl]-2-hydroxy-4-oxobut-2-enoic acid
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inhibition of duplex DNA-unwinding activity
(2Z)-4-[3-[(4-chlorobenzyl)oxy]phenyl]-2-hydroxy-4-oxobut-2-enoic acid
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inhibition of duplex DNA-unwinding activity
(2Z)-4-[4-(benzyloxy)phenyl]-2-hydroxy-4-oxobut-2-enoic acid
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low inhibitory activities, para-relationship between the diketoacid moiety and the OCH2Ar group do not show antiviral activities
(2Z)-4-[4-[(4-chlorobenzyl)oxy]phenyl]-2-hydroxy-4-oxobut-2-enoic acid
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low inhibitory activities, para-relationship between the diketoacid moiety and the OCH2Ar group do not show antiviral activities
(5'R)-8,5'-cyclo-2'-deoxyguanosine
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the enzyme is strongly inhibited by (5'R)-8,5'-cyclo-2'-deoxyguanosine in the non-translocating strand
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(5'S)-8,5'-cyclo-2'-deoxyguanosine
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the enzyme is strongly inhibited by (5'S)-8,5'-cyclo-2'-deoxyguanosine in the non-translocating strand. At 40 nM enzyme, less than 10% of the forked duplex with (5'S)-8,5'-cyclo-2'-deoxyguanosine in the nontranslocating strand is unwound compared to 60% of the control forked duplex or the substrate with (5'S)-8,5'-cyclo-2'-deoxyguanosine in the translocating strand
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(NH4)2SO4
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45 mM
2',3'-ddATP
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inhibition of NTPase activity of NS3 protein by NTP derivatives
2',3'-ddGTP
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inhibition of NTPase activity of NS3 protein by NTP derivatives
2',3'-ddTTP
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inhibition of NTPase activity of NS3 protein by NTP derivatives
2'-dATP
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inhibition of NTPase activity of NS3 protein by NTP derivatives
2'-deoxythymidine 5'-phosphoryl-beta,gamma-hypophosphate
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i.e. ppopT, dTTP analogue, most efficient inhibitor of NTPase activity among nucleotide derivaties, inhibits the ATP-dependent helicase reaction and also the ATP-independent duplex unwinding, structure of nucleic base and ribose fragment of NTP molecule have a slight effects on inhibitory properties
2'-dGTP
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inhibition of NTPase activity of NS3 protein by NTP derivatives
2'-dTTP
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inhibition of NTPase activity of NS3 protein by NTP derivatives
3'-dATP
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inhibition of NTPase activity of NS3 protein by NTP derivatives
3'-dGTP
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inhibition of NTPase activity of NS3 protein by NTP derivatives
3'-dUTP
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inhibition of NTPase activity of NS3 protein by NTP derivatives
5-fluoro-2-selenocytosine
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reduces ATPase activity, no effect on helicase activity
Aclarubicin
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actinomycin
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actinomycin C1
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ADP
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inhibition of NTPase activity of NS3 protein by NTP derivatives
ammonium sulfate
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45 mM, complete inhibition
AMP
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inhibition of NTPase activity of NS3 protein by NTP derivatives
ATPgammaS
benzoquinoquinoxaline
BQQ, inhibits ChlR1 triplex DNA unwinding activity
beta,gamma-methylene-ATP
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efficient inhibitor, like the N1-oxides N1-oxoadenosine 5'-triphosphate and N1-hydroxyinosine 5'-triphosphate
Cdc6-1 protein
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inhibits the DNA unwinding activity, although it strongly stimulates the interaction of the enzyme with bubble containing synthetic oligonucleotides
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Cdc6-3 protein
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inhibits the DNA unwinding activity, although it strongly stimulates the interaction of the enzyme with bubble containing synthetic oligonucleotides
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daunorubicin
DnaG primase
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SsoDnaG primase concentrations less than 0.001mM show little or no inhibition of SsoMCM helicase unwinding activity. Unwinding inhibition is strongest at or above 0.002 mM where the SsoMCM:SsoDnaG ratio is 2:1
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double-strand DNA binding protein
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doxorubicin
dsDNA
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0.01 mM
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Ethidium bromide
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histone H1
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0.001 mg/ml, inhibits of the DNA helicase activity
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Imidodiphosphate
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maximal inhibitory activity among diphosphate analogues, non-catalytic and catalytic conditions, inhibits the ATP-dependent helicase reaction but no effect on the ATP-independent duplex unwinding, structure of nucleic base and ribose fragment of NTP molecule have a slight effects on inhibitory properties
K+
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activation at 100-300 mM, inhibition above 500 mM
M13 dsDNA
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0.03 mM, complete inhibition
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M13 ssDNA
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0.03 mM, complete inhibition
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M13mp19 ssDNA
ATPase activity is slightly stimulated by ssDNA, and only M13mp19 ssDNA stimulates it significantly (increase in Vmax)
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N1-hydroxyinosine 5'-triphosphate
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inhibition of NTPase activity of NS3 protein by NTP derivatives
N1-O-ATP
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N1-OH-ITP
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N1-oxoadenosine 5'-triphosphate
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inhibition of NTPase activity of NS3 protein by NTP derivatives
Na+
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activation at 100-300 mM, inhibition above 500 mM
Nogalamycin
O6-benzyl-N7-chloroethylguanine
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weak inhibitor of the ATPase and helicase activity
O6-benzylguanine
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weak inhibitor of the ATPase and helicase activity
Poly(A)
moderately inhibits ATPase activity
poly(C)
moderately inhibits ATPase activity
Poly(U)
moderately inhibits ATPase activity
potassium phosphate
replication protein A
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inhibits unwinding and annealing activities
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ribavirin 5'-triphosphate
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competitive inhibitor with regard to ATP
RNA
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0.01 mM
single-strand DNA binding protein
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single-stranded binding protein
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MtbSSB, physical interaction between single-stranded binding protein of Mycobacterium tuberculosis, MtbSSB, and MtbDnaB. The helicase activity of MtbDnaB is stimulated by MtbSSB at low concentrations and inhibited at high concentrations. ssDNA-stimulated ATPase activity of DnaB can be inhibited in the presence of SSB, possibly due to the inability of DnaB to bind to the SSB-bound ssDNA
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single-stranded DNA
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single-stranded DNA-binding proteins
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SsoCdc6-1 protein
SsoCdc6-2 protein
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i.e. Cdc6 (cell-division control)-like factor from Sulfolobus solfataricus. The Cdc6 WH-domain is responsible for DNA-binding and inhibition of MCM DNA helicase. Residues 298-400 of Cdc6 (cell-division control)-like factor also bind DNA molecules and inhibit the DNA helicase activity of the SsoMCM mini-chromosome maintenance complex, although with lesser efficiency with respect to the full-sized SsoCdc6-2
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SsoCdc6-3 protein
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significantly inhibits the loading activity of the helicase, and this inhibitive effects can not be reversed by the stimulation of SsoCdc6-2 protein
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Streptavidin
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the enzyme is completely blocked by streptavidin bound to the 3'-ssDNA tail 6 nucleotides upstream of the single-stranded/double-stranded DNA junction. The enzyme efficiently unwinds the forked duplex with streptavidin bound just upstream of the junction, suggesting that the enzyme recognizes elements of the fork structure to initiate unwinding
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TaGins51 protein
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inhibits the ATPase activity, but not the helicase activity
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tetrabromobenzotriazole
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inhibits unwinding, no inhibition of ATP hydrolysis
Tim protein
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the Tim protein alone also decreases the ATPase and DNA helicase activities of the Mcm 4/6/7 complex
Tim-Tipin complex
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the addition of the human Tim-Tipin complex inhibits both ATPase and DNA helicase activities of the Mcm4/6/7 complex. The ATPase activity in the presence of ssDNA appears to be affected more severely compared with that seen in the absence of ssDNA. The Tim protein alone also decreases the ATPase and DNA helicase activities of the Mcm 4/6/7 complex, whereas Tipin does not
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Trypsin
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UTP
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inhibition of NTPase activity of NS3 protein by NTP derivatives
yeast total RNA
severly inhibits ATPase activity
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additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
ATP
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catalytic DNA helicase activity coupled with NTPase stimulated by
DNA
ATPase activity is stimulated by yeast genomic DNA and salmon sperm DNA
DnaG primase
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interaction of Sulfolobus solfataricus DnaG primase (SsoDnaG) with the replicative minichromosome maintenance helicase (SsoMCM) on DNA.The complex of SsoDnaG with SsoMCM stimulates the ATPase activity of SsoMCM but leaves the priming activity of SsoDnaG unchanged
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Double-stranded DNA
dsDNA
ATPase activity of StoHerA is stimulated by ssDNA and dsDNA
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GINS complex
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stimulates both the ATPase and DNA helicase activities of mini-chromosome maintenance helicase; the DNA helicase activity of Pyrococcus furiosus MCM is stimulated by the addition of the Pyrococcus furiosus GINS complex of Gins23 and Gins51
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heterotrimeric single-stranded DNA binding protein replication protein A
enhances DNA helicase activity of Mph1
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homopolynucleotides
significantly stimulate the ATPase activity (15-25fold) with the exception of poly(G) and poly(dG), which are non-stimulatory. dT24 binds over 10 times more strongly than dA24
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mitochondrial single-stranded DNA-binding protein
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stimultes the enzyme
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N7-chloroethylguanine
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; 2.2fold activation at 200-250 mM
N9-chloroethylguanine
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8.5fold activation at 200-250 mM
O6-benzyl-N9-chloroethylguanine
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stimulator of NTPase activity, with a maximum effect of 350% of control at 650 mM
poly(C)
strong stimulation
poly(dA)
poly(dI*C)
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weakly supports ATPase activity
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Poly(dT)
Poly(U)
strong stimulation
polyadenylate
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doubling of ATPase activity in the presence of
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polyuridylate
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doubling of ATPase activity in the presence of, lowers Km for the ATP substrate
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repair proteins Mre11
stimulates helicase activity
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replication protein A
ribavirin
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activates ATPase activity, no effect on helicase activity
single-stranded binding protein
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MtbSSB, physical interaction between single-stranded binding protein of Mycobacteri