D
IPR012310

DNA ligase, ATP-dependent, central

InterPro entry
Short nameDNA_ligase_ATP-dep_cent
domain relationships

Description

DNA ligase (polydeoxyribonucleotide synthase) is the enzyme that joins two DNA fragments by catalysing the formation of an internucleotide ester bond between phosphate and deoxyribose. It is active during DNA replication, DNA repair and DNA recombination. There are two forms of DNA ligase, one requires ATP (
6.5.1.1
), the other NAD (
6.5.1.2
), the latter being restricted to eubacteria. Eukaryotic, archaebacterial, viral and some eubacterial DNA ligases are ATP-dependent. The first step in the ligation reaction is the formation of a covalent enzyme-AMP complex. The co-factor ATP is cleaved to pyrophosphate and AMP, with the AMP being covalently joined to a highly conserved lysine residue in the active site of the ligase. The activated AMP residue is then transferred to the 5'phosphate of the nick, before the nick is sealed by phosphodiester-bond formation and AMP elimination
[5, 2]
.

This domain belongs to a more diverse superfamily, including catalytic domain of the mRNA capping enzyme (
IPR001339
) and NAD-dependent DNA ligase (
IPR001679
)
[3]
.

Vertebrate cells encode three well-characterised DNA ligases (DNA ligases I, III and IV), all of which are related in structure and sequence. With the exception of the atypically small PBCV-1 viral enzyme, two regions of primary sequence are common to all members of the family. The catalytic region comprises six conserved sequence motifs (I, III, IIIa, IV, V-VI), motif I includes the lysine residue that is adenylated in the first step of the ligation reaction. The function of the second, less well-conserved region is unknown. When folded, each protein comprises of two distinct sub-domains: a large amino-terminal sub-domain ('domain 1') and a smaller carboxy-terminal sub-domain ('domain 2'). The ATP-binding site of the enzyme lies in the cleft between the two sub-domains. Domain 1 consists of two antiparallelβ-sheets flanked by α-helices, whereas domain 2 consists of a five-stranded β-barrel and a single α-helix, which form the oligonucleotide-binding fold
[1, 4]
.

References

1.Molecular characterisation of a DNA ligase gene of the extremely thermophilic archaeon Desulfurolobus ambivalens shows close phylogenetic relationship to eukaryotic ligases. Kletzin A. Nucleic Acids Res. 20, 5389-96, (1992). View articlePMID: 1437556

2.Mammalian DNA ligases. Lindahl T, Barnes DE. Annu. Rev. Biochem. 61, 251-81, (1992). View articlePMID: 1497311

3.Crystal structure of an ATP-dependent DNA ligase from bacteriophage T7. Subramanya HS, Doherty AJ, Ashford SR, Wigley DB. Cell 85, 607-15, (1996). View articlePMID: 8653795

4.ATP-dependent DNA ligases. Martin IV, MacNeill SA. Genome Biol. 3, REVIEWS3005, (2002). View articlePMID: 11983065

5.Location of the active site for enzyme-adenylate formation in DNA ligases. Tomkinson AE, Totty NF, Ginsburg M, Lindahl T. Proc. Natl. Acad. Sci. U.S.A. 88, 400-4, (1991). View articlePMID: 1988940

GO terms

Cross References

Contributing Member Database Entries
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