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Information on EC 6.5.1.2 - DNA ligase (NAD+) and Organism(s) Enterococcus faecalis and UniProt Accession Q837V6

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EC Tree
IUBMB Comments
The enzyme, typically found in bacteria, catalyses the ligation of DNA strands with 3'-hydroxyl and 5'-phosphate termini, forming a phosphodiester and sealing certain types of single-strand breaks in duplex DNA. Catalysis occurs by a three-step mechanism, starting with the activation of the enzyme by NAD+, forming a phosphoramide bond between adenylate and a lysine residue. The adenylate group is then transferred to the 5'-phosphate terminus of the substrate, forming the capped structure 5'-(5'-diphosphoadenosine)-[DNA]. Finally, the enzyme catalyses a nucleophilic attack of the 3'-OH terminus on the capped terminus, which results in formation of the phosphodiester bond and release of the adenylate. RNA can also act as substrate, to some extent. cf. EC 6.5.1.1, DNA ligase (ATP), EC 6.5.1.6, DNA ligase (ATP or NAD+), and EC 6.5.1.7, DNA ligase (ATP, ADP or GTP).
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Enterococcus faecalis
UNIPROT: Q837V6
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The taxonomic range for the selected organisms is: Enterococcus faecalis
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
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ATP
+
(deoxyribonucleotide)n-3'-hydroxyl
+
5'-phospho-(deoxyribonucleotide)m
=
(deoxyribonucleotide)n+m
+
AMP
+
beta-nicotinamide D-nucleotide
+
+
5'-phospho-(deoxyribonucleotide)m
=
+
+
beta-nicotinamide D-nucleotide
Synonyms
nad(+)-dependent dna ligase, taq dna ligase, nad+-dependent dna ligase, tfi dna ligase, nad-dependent dna ligase, tth dna ligase, mimilig, mtuliga, wbm-liga, polynucleotide synthetase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
NAD+-dependent DNA ligase
-
Deoxyribonucleate ligase
-
-
-
-
Deoxyribonucleic acid joinase
-
-
-
-
Deoxyribonucleic acid ligase
-
-
-
-
Deoxyribonucleic joinase
-
-
-
-
Deoxyribonucleic ligase
-
-
-
-
Deoxyribonucleic repair enzyme
-
-
-
-
Deoxyribonucleic-joining enzyme
-
-
-
-
DNA joinase
-
-
-
-
DNA ligase
DNA ligase (NAD)
-
-
-
-
DNA repair enzyme
-
-
-
-
DNA-joining enzyme
-
-
-
-
Ligase, polynucleotide (nicotinamide adenine dinucleotide)
-
-
-
-
NAD+-dependent DNA ligase
-
-
Polydeoxyribonucleotide synthase (NAD+)
-
-
-
-
Polydeoxyribonucleotide synthase [NAD+]
-
-
-
-
Polynucleotide ligase
-
-
-
-
Polynucleotide synthetase
-
-
-
-
Polynucleotide synthetase (nicotinamide adenine dinucleotide)
-
-
-
-
Synthetase, polydeoxyribonucleotide (nicotinamide adenine dinucleotide)
-
-
-
-
Tfi DNA ligase
-
-
-
-
Tth DNA ligase
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
poly(deoxyribonucleotide)-3'-hydroxyl:5'-phospho-poly(deoxyribonucleotide) ligase (NAD+)
The enzyme, typically found in bacteria, catalyses the ligation of DNA strands with 3'-hydroxyl and 5'-phosphate termini, forming a phosphodiester and sealing certain types of single-strand breaks in duplex DNA. Catalysis occurs by a three-step mechanism, starting with the activation of the enzyme by NAD+, forming a phosphoramide bond between adenylate and a lysine residue. The adenylate group is then transferred to the 5'-phosphate terminus of the substrate, forming the capped structure 5'-(5'-diphosphoadenosine)-[DNA]. Finally, the enzyme catalyses a nucleophilic attack of the 3'-OH terminus on the capped terminus, which results in formation of the phosphodiester bond and release of the adenylate. RNA can also act as substrate, to some extent. cf. EC 6.5.1.1, DNA ligase (ATP), EC 6.5.1.6, DNA ligase (ATP or NAD+), and EC 6.5.1.7, DNA ligase (ATP, ADP or GTP).
CAS REGISTRY NUMBER
COMMENTARY hide
37259-52-2
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
NAD+ + (deoxyribonucleotide)n + (deoxyribonucleotide)m
AMP + beta-nicotinamide D-ribonucleotide + (deoxyribonucleotide)n+m
show the reaction diagram
-
-
-
?
NAD+ + (deoxyribonucleotide)n + (deoxyribonucleotide)m
AMP + nicotinamide nucleotide + (deoxyribonucleotide)n+m
show the reaction diagram
-
-
-
?
NAD+ + (deoxyribonucleotide)n + (deoxyribonucleotide)m
AMP + nicotinamide nucleotide + (deoxyribonucleotide)n+m
show the reaction diagram
-
in addition to the unique N-terminal domain Ia that stimulates ligase-AMP formation, there are three C-terminal domains that extend from the OB domain: a small zinc-binding (Zn) domain, a helix-hairpin-helix domain, and a BRCA1 C-terminal domain
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-methylthio-ATP
potent inhibitor
(2R,3R,4S,5R)-2-[6-amino-2-(cyclopentyloxy)-9H-purin-9-yl]-5-(hydroxymethyl)tetrahydrofuran-3,4-diol
-
-
2-bromo-4-(phenylamino)thieno[3,2-c]pyridine-7-carboxamide
-
-
2-bromo-4-(propylamino)thieno[3,2-c]pyridine-7-carboxamide
-
-
2-bromo-4-[(2-hydroxyethyl)amino]thieno[3,2-c]pyridine-7-carboxamide
-
-
4-amino-2-(1H-pyrazol-5-yl)thieno[3,2-c]pyridine-7-carboxamide
-
-
4-amino-2-bromo-3-methylthieno[3,2-c]pyridine-7-carboxamide
-
-
4-amino-2-bromothieno[3,2-c]pyridine-7-carboxamide
-
-
4-amino-2-methylthieno[3,2-c]pyridine-7-carboxamide
-
-
4-amino-3-(1H-pyrazol-5-yl)thieno[3,2-c]pyridine-7-carboxamide
-
-
4-amino-3-bromothieno[3,2-c]pyridine-7-carboxamide
-
-
4-amino-3-methylthieno[3,2-c]pyridine-7-carboxamide
-
-
4-amino-N2-ethylthieno[3,2-c]pyridine-2,7-dicarboxamide
-
-
4-aminothieno[3,2-c]pyridine-2,7-dicarboxamide
-
-
4-aminothieno[3,2-c]pyridine-3,7-dicarboxamide
-
-
4-aminothieno[3,2-c]pyridine-7-carboxamide
-
-
ethyl 4-amino-7-carbamoylthieno[3,2-c]pyridine-2-carboxylate
-
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0005
2-methylthio-ATP
Enterococcus faecalis
-
0.16
2-bromo-4-(phenylamino)thieno[3,2-c]pyridine-7-carboxamide
Enterococcus faecalis
-
pH and temperature not specified in the publication
0.13
2-bromo-4-(propylamino)thieno[3,2-c]pyridine-7-carboxamide
Enterococcus faecalis
-
pH and temperature not specified in the publication
0.2
2-bromo-4-[(2-hydroxyethyl)amino]thieno[3,2-c]pyridine-7-carboxamide
Enterococcus faecalis
-
value above, pH and temperature not specified in the publication
0.1
4-amino-2-(1H-pyrazol-5-yl)thieno[3,2-c]pyridine-7-carboxamide
Enterococcus faecalis
-
pH and temperature not specified in the publication
0.0081
4-amino-2-bromo-3-methylthieno[3,2-c]pyridine-7-carboxamide
Enterococcus faecalis
-
pH and temperature not specified in the publication
0.077
4-amino-2-bromothieno[3,2-c]pyridine-7-carboxamide
Enterococcus faecalis
-
pH and temperature not specified in the publication
0.2
4-amino-2-methylthieno[3,2-c]pyridine-7-carboxamide
Enterococcus faecalis
-
value above, pH and temperature not specified in the publication
0.2
4-amino-3-(1H-pyrazol-5-yl)thieno[3,2-c]pyridine-7-carboxamide
Enterococcus faecalis
-
value above, pH and temperature not specified in the publication
0.13
4-amino-3-bromothieno[3,2-c]pyridine-7-carboxamide
Enterococcus faecalis
-
pH and temperature not specified in the publication
0.2
4-amino-3-methylthieno[3,2-c]pyridine-7-carboxamide
Enterococcus faecalis
-
value above, pH and temperature not specified in the publication
0.2
4-amino-N2-ethylthieno[3,2-c]pyridine-2,7-dicarboxamide
Enterococcus faecalis
-
value above, pH and temperature not specified in the publication
0.034
4-aminothieno[3,2-c]pyridine-2,7-dicarboxamide
Enterococcus faecalis
-
pH and temperature not specified in the publication
0.2
4-aminothieno[3,2-c]pyridine-3,7-dicarboxamide
Enterococcus faecalis
-
value above, pH and temperature not specified in the publication
0.2
4-aminothieno[3,2-c]pyridine-7-carboxamide
Enterococcus faecalis
-
value above, pH and temperature not specified in the publication
0.074
ethyl 4-amino-7-carbamoylthieno[3,2-c]pyridine-2-carboxylate
Enterococcus faecalis
-
pH and temperature not specified in the publication
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystals of adenylation domain are grown by vapor diffusion using hanging drops. Crystals belong to space group C2 with unit cell parameters of a = 90.2 A, b = 86.1 A, c = 57.1 A and beta = 101°. Visualization of NAD+ recognition by an NAD+-dependent ligase
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
adenylation domain
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
NAD+-dependent ligases can serve as a valuable target in the development of chemotherapeutics for the treatment of numerous human ailments
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Gajiwala, K.S.; Pinko, C.
Structural rearrangement accompanying NAD+ synthesis within a bacterial DNA ligase crystal
Structure
12
1449-1459
2004
Enterococcus faecalis (Q837V6)
Manually annotated by BRENDA team
Tomkinson, A.E.; Vijayakumar, S.; Pascal, J.M.; Ellenberger, T.
DNA ligases: Structure, reaction mechanism, and function
Chem. Rev.
106
687-699
2006
Enterococcus faecalis (Q837V6), Thermus filiformis (Q9ZHI0)
Manually annotated by BRENDA team
Pascal, J.M.
DNA and RNA ligases: structural variations and shared mechanisms
Curr. Opin. Struct. Biol.
18
96-105
2008
Escherichia coli, Enterococcus faecalis, Thermus filiformis
Manually annotated by BRENDA team
Dwivedi, N.; Dube, D.; Pandey, J.; Singh, B.; Kukshal, V.; Ramachandran, R.; Tripathi, R.P.
NAD+-dependent DNA ligase: a novel target waiting for the right inhibitor
Med. Res. Rev.
28
545-568
2008
Escherichia coli, Geobacillus stearothermophilus (O87703), Mycobacterium tuberculosis (P9WNV1), Enterococcus faecalis (Q837V6), Thermus filiformis (Q9ZHI0), Mycobacterium tuberculosis H37Rv (P9WNV1)
Manually annotated by BRENDA team
Shuman, S.
DNA ligases: progress and prospects
J. Biol. Chem.
284
17365-17369
2009
Escherichia coli (P15042), Enterococcus faecalis (Q837V6)
Manually annotated by BRENDA team
Murphy-Benenato, K.; Wang, H.; McGuire, H.M.; Davis, H.E.; Gao, N.; Prince, D.B.; Jahic, H.; Stokes, S.S.; Boriack-Sjodin, P.A.
Identification through structure-based methods of a bacterial NAD(+)-dependent DNA ligase inhibitor that avoids known resistance mutations
Bioorg. Med. Chem. Lett.
24
360-366
2014
Streptococcus pneumoniae, Enterococcus faecalis, Haemophilus influenzae, Staphylococcus aureus
Manually annotated by BRENDA team