Information on EC 3.1.11.7 - adenosine-5'-diphospho-5'-[DNA] diphosphatase

Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Select one or more organisms in this record:

The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
3.1.11.7
-
RECOMMENDED NAME
GeneOntology No.
adenosine-5'-diphospho-5'-[DNA] diphosphatase
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
adenosine-5'-diphospho-5'-(ribonucleotide)-[DNA] + H2O = AMP + 5'-phospho-(ribonucleotide)-[DNA]
show the reaction diagram
(2)
-
-
-
adenosine-5'-diphospho-5'-[DNA] + H2O = AMP + phospho-5'-[DNA]
show the reaction diagram
(1)
-
-
-
SYSTEMATIC NAME
IUBMB Comments
adenosine-5'-diphospho-5'-[DNA] hydrolase (adenosine 5'-phosphate-forming)
Aprataxin is a DNA-binding protein involved in different types of DNA break repair. The enzyme acts (among other activities) on abortive DNA ligation intermediates that contain an adenylate covalently linked to the 5'-phosphate DNA terminus. It also acts when the adenylate is covalently linked to the 5'-phosphate of a ribonucleotide linked to a DNA strand, which is the result of abortive ligase activty on products of EC 3.1.26.4, ribonuclease H, an enzyme that cleaves RNA-DNA hybrids on the 5' side of the ribonucleotide found in the 5'-RNA-DNA-3' junction. Aprataxin binds the adenylate group to a histidine residue within the active site, followed by its hydrolysis from the nucleic acid and eventual release, leaving a 5'-phosphate terminus that can be efficiently rejoined. The enzyme also possesses the activities of EC 3.1.11.8, guanosine-5'-diphospho-5'-[DNA] diphosphatase, and EC 3.1.12.2, DNA-3'-diphospho-5'-guanosine diphosphatase.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
adenosine-5'-diphospho-5'-(ribonucleotide)-[DNA] + H2O
AMP + 5'-phospho-(ribonucleotide)-[DNA]
show the reaction diagram
adenosine-5'-diphospho-5'-[DNA] + H2O
AMP + phospho-5'-[DNA]
show the reaction diagram
adenosine-5'-monophosphoramidate + H2O
AMP + NH3
show the reaction diagram
-
-
-
-
?
ATP + H2O
AMP + diphosphate
show the reaction diagram
-
-
-
-
?
P1,P3-bis(5'-adenosyl)triphosphate + H2O
AMP + ADP
show the reaction diagram
-
-
-
-
?
P1,P4-bis(5'-adenosyl)tetraphosphate + H2O
?
show the reaction diagram
-
-
-
-
?
P1,P4-bis(5'-adenosyl)tetraphosphate + H2O
AMP + ATP
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
adenosine-5'-diphospho-5'-(ribonucleotide)-[DNA] + H2O
AMP + 5'-phospho-(ribonucleotide)-[DNA]
show the reaction diagram
adenosine-5'-diphospho-5'-[DNA] + H2O
AMP + phospho-5'-[DNA]
show the reaction diagram
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Duplex DNA
-
significantly reduces catalytic catalytic activity on the model histidine triad nucleotide-binding protein substrate, AMPNH2, and the Fragile histidine triad protein substrate, Ap4A
-
single-strand DNA
-
reduces catalytic catalytic activity on the model histidine triad nucleotide-binding protein substrate, AMPNH2, and the Fragile histidine triad protein substrate, Ap4A
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0000166 - 0.00111
adenosine-5'-diphospho-5'-(ribonucleotide)-[DNA]
-
0.000112 - 0.00247
adenosine-5'-diphospho-5'-[DNA]
-
0.837
adenosine-5'-monophosphoramidate
-
pH 7.0, 30C
-
0.021
P1,P3-bis(5'-adenosyl)triphosphate
-
pH 7.2, 22C
0.018 - 0.039
P1,P4-bis(5'-adenosyl)tetraphosphate
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.23 - 0.31
adenosine-5'-diphospho-5'-(ribonucleotide)-[DNA]
-
0.32 - 0.37
adenosine-5'-diphospho-5'-[DNA]
-
0.0195
adenosine-5'-monophosphoramidate
-
pH 7.0, 30C
-
0.00008
P1,P3-bis(5'-adenosyl)triphosphate
-
pH 7.2, 22C
0.0009 - 0.0115
P1,P4-bis(5'-adenosyl)tetraphosphate
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
21 - 19000
adenosine-5'-diphospho-5'-(ribonucleotide)-[DNA]
-
13 - 3000
adenosine-5'-diphospho-5'-[DNA]
-
0.0038
P1,P3-bis(5'-adenosyl)triphosphate
-
pH 7.2, 22C
0.023
P1,P4-bis(5'-adenosyl)tetraphosphate
-
pH 7.2, 22C
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
primary neural cell
Manually annotated by BRENDA team
additional information
-
aprataxin is ubiquitously expressed
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
aprataxin forkhead-associated domain and modeling of the pSDpTD peptide into the apo structure. pT recognition is provided by residues Arg29 and Ser41
-
structure-function studies of human Aptx in complex with RNA-DNA, AMP and Zn2+
-
crystal structure in complex with GMP, to 1.5 A resolution. GMP binds at the same position and in the same anti nucleoside conformation as AMP, and aprataxin makes more extensive nucleobase contacts with guanine than with adenine, via a hydrogen bonding network to the guanine O6, N1, N2 base edge
-
structure of APTX in complex with DNA, AMP and Zn2+ reveals active site and DNA interaction clefts formed by fusing a histidine triad nucleotide hydrolase with an DNA minor groove binding C2HE Zn-finger. An Aptx helical wedge interrogates the base stack for DNA end/nick sensing. Histidine triad nucleotide hydrolase, Zn-finger, the wedge, and an [F/Y]PK pivot motif cooperate to distort terminal DNA base-pairing and direct 5'-AMP into the active site pocket
-
structures of apo form and in complex with dsDNA and dsDNA-AMP. The bound DNA adopts a 5'-flap conformation that facilitates 5'-AMP access to the active site, where AMP cleavage occurs by a canonical catalytic mechanism
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
-
expression in Saccharomyces cerevisiae
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
of the two splicing variants of APTX mRNA, the short and the long forms, long-form APTX mRNA is the major isoform
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
689insT
-
recessive mutation associated with ataxia and oculomotor apraxia, huge loss in protein stability
840delT
-
recessive mutation associated with ataxia and oculomotor apraxia, huge loss in protein stability
A198V
-
recessive mutation associated with ataxia and oculomotor apraxia, huge loss in protein stability
D267G
-
recessive mutation associated with ataxia and oculomotor apraxia, huge loss in protein stability
H260A
-
recessive mutation associated with ataxia and oculomotor apraxia, huge loss in protein stability
P206L
-
recessive mutation associated with ataxia and oculomotor apraxia, huge loss in protein stability
R199H
-
recessive mutation associated with ataxia and oculomotor apraxia, protein retains substantial function, consistent with altered activity
R29A
-
mutation of forkhead-associated domain residue, prevents its interaction with mediator of DNA-damage checkpoint protein MDC1 and recruitment to sites of DNA damage
T739C
FLJ20157
homozygous mutation idientified in a patient with ataxia-oculomotor apraxia type 1
W279R
-
recessive mutation associated with ataxia and oculomotor apraxia, huge loss in protein stability
W279X
-
recessive mutation associated with ataxia and oculomotor apraxia, huge loss in protein stability
H138A
-
mutation significantly impairs deadenylation activity
H147N
-
complete loss of activity
S168A
-
mutation significantly impairs deadenylation activity
H138A
-
mutation significantly impairs deadenylation activity
-
H147N
-
complete loss of activity
-
S168A
-
mutation significantly impairs deadenylation activity
-
additional information
-
removal of the N-terminal forkhead associated domain does not alter activity with substrates AMPNH2 and Ap4A
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine