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Information on EC 6.5.1.6 - DNA ligase (ATP or NAD+)

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IUBMB Comments
The enzymes from the archaea Thermococcus fumicolans and Thermococcus onnurineus show high activity with either ATP or NAD+, and significantly lower activity with TTP, GTP, and CTP. The enzyme 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 ATP or 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. Different from EC 6.5.1.1, DNA ligase (ATP), EC 6.5.1.2, DNA ligase (NAD+) and EC 6.5.1.7, DNA ligase (ATP, ADP or GTP).
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The expected taxonomic range for this enzyme is: Thermococcus
Reaction Schemes
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Synonyms
tfu dna ligase, more
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
(deoxyribonucleotide)n-3'-hydroxyl + 5'-(5'-diphosphoadenosine)-(deoxyribonucleotide)m = (deoxyribonucleotide)n+m + AMP
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(1c); (2c); catalytic reaction mechanism, detailed overview
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5'-adenosyl [DNA ligase]-Nepsilon-phosphono-L-lysine + 5'-phospho-(deoxyribonucleotide)m = 5'-(5'-diphosphoadenosine)-(deoxyribonucleotide)m + [DNA ligase]-L-lysine
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(1b); (2b)
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ATP + (deoxyribonucleotide)n-3'-hydroxyl + 5'-phospho-(deoxyribonucleotide)m = (deoxyribonucleotide)n+m + AMP + beta-nicotinamide D-nucleotide
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ATP + (deoxyribonucleotide)n-3'-hydroxyl + 5'-phospho-(deoxyribonucleotide)m = (deoxyribonucleotide)n+m + AMP + diphosphate
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ATP + [DNA ligase]-L-lysine = 5'-adenosyl [DNA ligase]-Nepsilon-phosphono-L-lysine + diphosphate
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(1a)
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NAD+ + [DNA ligase]-L-lysine = 5'-adenosyl [DNA ligase]-Nepsilon-phosphono-L-lysine + beta-nicotinamide D-nucleotide
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(2a)
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