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PDBsum entry 1tae
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protein ligands metals Protein-protein interface(s) links
Ligase PDB id
1tae

 

 

 

 

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Contents
Protein chains
321 a.a. *
Ligands
SO4 ×24
NAD ×4
Metals
_NA ×2
Waters ×176
* Residue conservation analysis
PDB id:
1tae
Name: Ligase
Title: Structural rearrangement accompanying NAD+ synthesis within a bacterial DNA ligase crystal
Structure: DNA ligase, NAD-dependent. Chain: a, b, c, d. Fragment: adenylation domain. Engineered: yes
Source: Enterococcus faecalis. Organism_taxid: 226185. Strain: v583. Gene: liga. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
2.70Å     R-factor:   0.204     R-free:   0.263
Authors: K.S.Gajiwala,C.Pinko
Key ref:
K.S.Gajiwala and C.Pinko (2004). Structural rearrangement accompanying NAD+ synthesis within a bacterial DNA ligase crystal. Structure, 12, 1449-1459. PubMed id: 15296738 DOI: 10.1016/j.str.2004.05.017
Date:
19-May-04     Release date:   23-Nov-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q837V6  (DNLJ_ENTFA) -  DNA ligase from Enterococcus faecalis (strain ATCC 700802 / V583)
Seq:
Struc: 		 
Seq:
Struc: 		676 a.a.
321 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.6.5.1.2  - Dna ligase (NAD(+)).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: NAD+ + (deoxyribonucleotide)n-3'-hydroxyl + 5'-phospho- (deoxyribonucleotide)m = (deoxyribonucleotide)n+m + AMP + beta- nicotinamide D-nucleotide
NAD(+)
Bound ligand (Het Group name = NAD)
corresponds exactly 		+ (deoxyribonucleotide)n-3'-hydroxyl
 + 5'-phospho- (deoxyribonucleotide)m
 = (deoxyribonucleotide)n+m
 + AMP
 + beta- nicotinamide D-nucleotide
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
DOI no: 10.1016/j.str.2004.05.017 Structure 12:1449-1459 (2004)
PubMed id: 15296738  
 
 
Structural rearrangement accompanying NAD+ synthesis within a bacterial DNA ligase crystal.
K.S.Gajiwala, C.Pinko.
 
  ABSTRACT  
 
DNA ligase is an enzyme important for DNA repair and replication. Eukaryotic genomes encode ligases requiring ATP as the cofactor; bacterial genomes encode NAD(+)-dependent ligase. This difference in substrate specificities and the essentiality of NAD(+)-dependent ligase for bacterial survival make NAD(+)-dependent ligase a good target for designing highly specific anti-infectives. Any such structure-guided effort would require the knowledge of the precise mechanism of NAD+ recognition by the enzyme. We report the principles of NAD+ recognition by presenting the synthesis of NAD+ from nicotinamide mononucleotide (NMN) and AMP, catalyzed by Enterococcus faecalis ligase within the crystal lattice. Unprecedented conformational change, required to reorient the two subdomains of the protein for the condensation to occur and to recognize NAD+, is captured in two structures obtained using the same protein crystal. Structural data and sequence analysis presented here confirms and extends prior functional studies of the ligase adenylation reaction.
 
  Selected figure(s)  
 
Figure 5.
Figure 5. NAD^+ Recognition by Ef LigaseSome of the interactions between polar atoms that are within 3.2 Å are shown with dashes.
 
  The above figure is reprinted by permission from Cell Press: Structure (2004, 12, 1449-1459) copyright 2004.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19913033 A.Piserchio, P.A.Nair, S.Shuman, and R.Ghose (2010).
Solution NMR studies of Chlorella virus DNA ligase-adenylate.
  J Mol Biol, 395, 291-308.  
20098496 J.D.Durrant, R.E.Amaro, L.Xie, M.D.Urbaniak, M.A.Ferguson, A.Haapalainen, Z.Chen, A.M.Di Guilmi, F.Wunder, P.E.Bourne, and J.A.McCammon (2010).
A multidimensional strategy to detect polypharmacological targets in the absence of structural and sequence homology.
  PLoS Comput Biol, 6, e1000648.  
19150981 L.K.Wang, H.Zhu, and S.Shuman (2009).
Structure-guided Mutational Analysis of the Nucleotidyltransferase Domain of Escherichia coli DNA Ligase (LigA).
  J Biol Chem, 284, 8486-8494.  
19690099 N.Tanaka, and S.Shuman (2009).
Structure-activity relationships in human RNA 3'-phosphate cyclase.
  RNA, 15, 1865-1874.  
20354588 R.V.Swift, and R.E.Amaro (2009).
Discovery and design of DNA and RNA ligase inhibitors in infectious microorganisms.
  Expert Opin Drug Discov, 4, 1281-1294.  
19329793 S.Shuman (2009).
DNA ligases: progress and prospects.
  J Biol Chem, 284, 17365-17369.  
18262407 J.M.Pascal (2008).
DNA and RNA ligases: structural variations and shared mechanisms.
  Curr Opin Struct Biol, 18, 96.  
18515356 L.K.Wang, P.A.Nair, and S.Shuman (2008).
Structure-guided Mutational Analysis of the OB, HhH, and BRCT Domains of Escherichia coli DNA Ligase.
  J Biol Chem, 283, 23343-23352.  
18795946 T.I.Meier, D.Yan, R.B.Peery, K.A.McAllister, C.Zook, S.B.Peng, and G.Zhao (2008).
Identification and characterization of an inhibitor specific to bacterial NAD+-dependent DNA ligases.
  FEBS J, 275, 5258-5271.  
17204483 A.Raymond, and S.Shuman (2007).
Deinococcus radiodurans RNA ligase exemplifies a novel ligase clade with a distinctive N-terminal module that is important for 5'-PO4 nick sealing and ligase adenylylation but dispensable for phosphodiester formation at an adenylylated nick.
  Nucleic Acids Res, 35, 839-849.  
17488851 H.Zhu, and S.Shuman (2007).
Characterization of Agrobacterium tumefaciens DNA ligases C and D.
  Nucleic Acids Res, 35, 3631-3645.  
17466627 J.Nandakumar, P.A.Nair, and S.Shuman (2007).
Last stop on the road to repair: structure of E. coli DNA ligase bound to nicked DNA-adenylate.
  Mol Cell, 26, 257-271.
PDB code: 2owo
17618295 P.A.Nair, J.Nandakumar, P.Smith, M.Odell, C.D.Lima, and S.Shuman (2007).
Structural basis for nick recognition by a minimal pluripotent DNA ligase.
  Nat Struct Mol Biol, 14, 770-778.
PDB codes: 2q2t 2q2u
17557328 S.K.Srivastava, D.Dube, V.Kukshal, A.K.Jha, K.Hajela, and R.Ramachandran (2007).
NAD+-dependent DNA ligase (Rv3014c) from Mycobacterium tuberculosis: novel structure-function relationship and identification of a specific inhibitor.
  Proteins, 69, 97.  
17938628 S.Shuman, and M.S.Glickman (2007).
Bacterial DNA repair by non-homologous end joining.
  Nat Rev Microbiol, 5, 852-861.  
16476729 D.Akey, A.Martins, J.Aniukwu, M.S.Glickman, S.Shuman, and J.M.Berger (2006).
Crystal structure and nonhomologous end-joining function of the ligase component of Mycobacterium DNA ligase D.
  J Biol Chem, 281, 13412-13423.
PDB code: 1vs0
17052461 J.M.Pascal, O.V.Tsodikov, G.L.Hura, W.Song, E.A.Cotner, S.Classen, A.E.Tomkinson, J.A.Tainer, and T.Ellenberger (2006).
A flexible interface between DNA ligase and PCNA supports conformational switching and efficient ligation of DNA.
  Mol Cell, 24, 279-291.
PDB codes: 2hii 2hik 2hiv 2hix
15671015 H.Zhu, and S.Shuman (2005).
Structure-guided mutational analysis of the nucleotidyltransferase domain of Escherichia coli NAD+-dependent DNA ligase (LigA).
  J Biol Chem, 280, 12137-12144.  
16199559 N.Keppetipola, and S.Shuman (2005).
Characterization of a thermophilic ATP-dependent DNA ligase from the euryarchaeon Pyrococcus horikoshii.
  J Bacteriol, 187, 6902-6908.  
16361267 S.K.Srivastava, D.Dube, N.Tewari, N.Dwivedi, R.P.Tripathi, and R.Ramachandran (2005).
Mycobacterium tuberculosis NAD+-dependent DNA ligase is selectively inhibited by glycosylamines compared with human DNA ligase I.
  Nucleic Acids Res, 33, 7090-7101.  
15901723 S.K.Srivastava, R.P.Tripathi, and R.Ramachandran (2005).
NAD+-dependent DNA Ligase (Rv3014c) from Mycobacterium tuberculosis. Crystal structure of the adenylation domain and identification of novel inhibitors.
  J Biol Chem, 280, 30273-30281.
PDB code: 1zau
15565146 J.M.Pascal, P.J.O'Brien, A.E.Tomkinson, and T.Ellenberger (2004).
Human DNA ligase I completely encircles and partially unwinds nicked DNA.
  Nature, 432, 473-478.
PDB code: 1x9n
15296724 S.Shuman (2004).
NAD+ specificity of bacterial DNA ligase revealed.
  Structure, 12, 1335-1336.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.

 

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