DNA ligase

spinqualitylabelsall models ATP-dependent DNA ligase complexed with ATP 2hix Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Function DNA ligase (LigD) is an enzyme which repairs single-stranded breaks in a double-stranded DNA. LigD is activated, in a species-dependent manner, by hydrolysis of ATP or NAD+. Mammalian LigD I ligates the nascent DNA of the lagging strand. LigD III complexes with XRCC1 in the process of nucleotide excision repair. LigD IV complexes with XRCC4 and catalyzes the last step in the non-homologous DNA end joining. See more details in ATP-Dependent DNA Ligase (Bacteriophage T7). Disease Known disease associated with this structure: DNA ligase I deficiency OMIM:[126391] The expression of DNA ligase I has been directly linked to cancer in humans. The enzyme is found most in proliferating cells and much less often in nondividing cells. In particular, in malignant tumors, the DNA ligase I enzyme was expressed much more compared to the DNA ligase I enzyme in normal tissues and their peripheral lymphocytes. Further experimentation showed that tumor cell growth rate was successfully decreased when antisense oligonucleotides targeting the mRNA of DNA ligase I were present. This suggests that DNA ligase I could be a good target for new anticancer studies. A specific point mutation (46BR in the mouse Lig1 gene) in DNA ligase I has also been linked as a cause for genome instability and cancer in humans. One possible reason for this is the accumulation of DNA fragments that are no longer ligated by the mutant DNA ligase I enzyme. Structural highlights Human LigD IV contains several domains: DNA-binding domain (residues 1-240); adenylation domain (residues 268-405) and the ca. 100 amino acid long BRCT motifs (residues 654-911). In the ATP-dependent LigD the ATP binds between 2 symmetry related LigD molecules. ATP binding site in ATP-dependent DNA ligase from S. solfataricus (2hix).

3D Structures of DNA ligase

Updated on 24-April-2017

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• ATP-dependent LigD
  • ATP-Dependent DNA Ligase (Bacteriophage T7), 2hix, 3ta7 – LigD N-terminal – Candidatus korarchaeum cryptofilum
    
  • 3gde – LigD – Archaeoglobus fulgidus
    
  • 2hiv – SsLigD – Sulfolobus solfataricus
    
  • 2hix - SsLigD + ATP
    
  • 2cfm - LigD + AMP – Pyrococcus furiosus
    
  • 2fao - PaLigD polymerase domain – Pseudomonas aeruginosa
    
  • 2faq, 2far - PaLigD polymerase domain + ATP + Mn
    
  • 1a0i – LigD + ATP – Bacteriophage T7
    
  • 4eq5 – LigD + AMP – Thermococcus sibiricus
    
  • 4d05 – LigD + AMP - Psychromonas
    
• NAD+-dependent LigD
  • 3jsl, 3jsn - SaLigD adenylation domain – Staphylococcus aureus
    
  • 4cc5, 4cc6, 5fpo, 5fpr – SaLigD adenylation domain + inhibitor
    
  • 3ba8, 3ba9, 3baa, 3bab, 3bac, 4eeq, 4efb, 4efe, 4lh6, 4lh7 - EfLigD adenylation domain + NMN + inhibitor – Enterococcus faecalis
    
  • 1ta8, 1tae - EfLigD adenylation domain
    
  • 1zau - MtLigD adenylation domain – Mycobacterium tuberculosis
    
  • 3sgi – MtLigD (mutant) + AMP
    
  • 1v9p, 1dgs – LigD – Thermos filiformis
    
  • 1b04 – LigD adenylation domain (mutant) – Geobacillus stearothermophilus
    
  • 4glw – LigD A + NMN + inhibitor – Streptococcus pneumoniae
    
  • 4glx – EcLigD + DNA + inhibitor - Escherichia coli
    
  • 5tt5 - EciLigD + NAD
    
  • 3pn1, 4uco, 4ucr, 4ucs, 4uct, 4ucu, 4ucv, 4ufz – HiLigD adenylation domain + inhibitor – Haemophilus influenza
    
  • 3uq8 - HiLigD adenylation domain + NAD
    
• LigD
  • 2q2t – CvLigD + DNA + AMP + CMP – Chlorella virus
    
  • 2q2u, 1p8l, 1fvi - CvLigD + DNA + mononucleotide
    
  • 2owo – LigD + DNA + AMP + CMP – Escherichia coli
    
  • 3qwu – LigD – Aquifex aeolicus
    
  • 1l7b – LigD BRCT domain – Thermos thermophilus - NMR
    
  • 3rr5 – LigD - Thermococcus
    
  • 5frq - LigD + DNA polymerase III subunit β – Helicobacter pylori
    
• Mammalian LigD I
  • 1x9n – hLigD I + DNA + AMP + CMP – human
    
  • 2od8 – LigD I residues 32-53 + PCNA
• Mammalian LigD III
  • 3l2p – hLigD III residues 257-833 + DNA
    
  • 1uw0 - hLigD III zinc-finger domain residues 1-117 – NMR
    
  • 1imo, 1in1 - hLigD III BRCTdomain – NMR
    
  • 3pc7 - hLigD III BRCTdomain
    
  • 3pc8 - hLigD III BRCTdomain (mutant) + XRCC1
    
  • 3qvg - hLigD III BRCTdomain + XRCC1
• Mammalian LigD IV
  • 3ii6, 1ik9 – hLigD IV C-terminal BRCT domains + DNA repair protein XRCC4
    
  • 3w5o - hLigD IV
    
  • 2e2w - hLigD IV BRCT domain - NMR
    
  • 1z56 – LigD IV + ligase interacting factor 1 - yeast
    
  • 3vnn - hLigD IV adenylation domain
    
  • 4hto - hLigD IV DNA-binding domain
    
  • 4htp - hLigD IV DNA-binding domain + artemis protein peptide
    
  • 3w1b, 3w1g - hLigD IV adenylation and DNA-binding domains + artemis protein peptide
    

References

Elevated expression of DNA ligase I in human cancers., Sun DY, Urrabaz R, Nguyen M, Marty J, Stringer S, Cruz E, Medina-Gundrum L, Weitman S., Clinical Cancer Research. 2001; 7(12):4143-4148.
Replication failure, genome instability, and increased cancer susceptibility in mice with a point mutation in the DNA ligase I gene., Harrison C, Ketchen AM, Redhead NJ, O'Sullivan MJ, Melton DW., Cancer Research. 2002; 62(14):4065-4074.

• Created with the participation of Audrey Kuan.

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