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Ligase PDB id
1fvi
Jmol
Contents
Protein chain
264 a.a. *
Ligands
SO4
AMP
Waters ×280
* Residue conservation analysis
PDB id:
1fvi
Name: Ligase
Title: Crystal structure of chlorella virus DNA ligase-adenylate
Structure: Chlorella virus DNA ligase-adenylate. Chain: a. Engineered: yes. Mutation: yes
Source: Chlorella virus. Organism_taxid: 10507. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Resolution:
2.00Å     R-factor:   0.190     R-free:   0.270
Authors: M.Odell,V.Sriskanda,S.Shuman,D.B.Nikolov
Key ref:
M.Odell et al. (2000). Crystal structure of eukaryotic DNA ligase-adenylate illuminates the mechanism of nick sensing and strand joining. Mol Cell, 6, 1183-1193. PubMed id: 11106756 DOI: 10.1016/S1097-2765(00)00115-5
Date:
20-Sep-00     Release date:   22-Nov-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
O41026  (O41026_PBCV1) -  ATP-dependent DNA ligase
Seq:
Struc: 		298 a.a.
264 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     DNA repair   3 terms 
  Biochemical function     nucleotide binding     5 terms  

 

 
DOI no: 10.1016/S1097-2765(00)00115-5 Mol Cell 6:1183-1193 (2000)
PubMed id: 11106756  
 
 
Crystal structure of eukaryotic DNA ligase-adenylate illuminates the mechanism of nick sensing and strand joining.
M.Odell, V.Sriskanda, S.Shuman, D.B.Nikolov.
 
  ABSTRACT  
 
Chlorella virus DNA ligase is the smallest eukaryotic ATP-dependent ligase known; it has an intrinsic nick-sensing function and suffices for yeast cell growth. Here, we report the 2.0 A crystal structure of the covalent ligase-AMP reaction intermediate. The conformation of the adenosine nucleoside and contacts between the enzyme and the ribose sugar have undergone a significant change compared to complexes of T7 ligase with ATP or mRNA capping enzyme with GTP. The conformational switch allows the 3' OH of AMP to coordinate directly the 5' PO(4) of the nick. The structure explains why nick sensing is restricted to adenylated ligase and why the 5' phosphate is required for DNA binding. We identify a metal binding site on ligase-adenylate and propose a mechanism of nick recognition and catalysis supported by mutational data.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. Overall Fold of the Chlorella Virus DNA Ligase–AdenylateThe figure was prepared with the program SETOR. The N-terminal domain 1 is colored in purple; the C-terminal domain 2 (an OB fold) is colored in cyan.(A) The lysyl–AMP adduct at the active site is shown.(B) The ligase molecule is oriented to highlight a sulfate bound on the surface of domain 1. 		Figure 6.
Figure 6. Surface Topology and ElectrostaticsThe space-filling surface images of the Chlorella virus ligase–adenylate were prepared with the program GRASP. Positive surface charge potential is shown in blue, and negative potential in red. The sulfate is colored green and the AMP is yellow.
 
  The above figures are reprinted by permission from Cell Press: Mol Cell (2000, 6, 1183-1193) copyright 2000.  
  Figures were 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.  
20837552 M.Englert, K.Sheppard, S.Gundllapalli, H.Beier, and D.Söll (2010).
Branchiostoma floridae has separate healing and sealing enzymes for 5'-phosphate RNA ligation.
  Proc Natl Acad Sci U S A, 107, 16834-16839.  
19636951 A.Piserchio, P.A.Nair, S.Shuman, and R.Ghose (2009).
Sequence-specific 1H N, 13C, and 15N backbone resonance assignments of the 34 kDa Paramecium bursaria Chlorella virus 1 (PBCV1) DNA ligase.
  Biomol NMR Assign, 3, 77-80.  
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.  
19850911 M.Issur, B.J.Geiss, I.Bougie, F.Picard-Jean, S.Despins, J.Mayette, S.E.Hobdey, and M.Bisaillon (2009).
The flavivirus NS5 protein is a true RNA guanylyltransferase that catalyzes a two-step reaction to form the RNA cap structure.
  RNA, 15, 2340-2350.  
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.  
18458338 A.Crut, P.A.Nair, D.A.Koster, S.Shuman, and N.H.Dekker (2008).
Dynamics of phosphodiester synthesis by DNA ligase.
  Proc Natl Acad Sci U S A, 105, 6894-6899.  
18562298 A.V.Cherepanov, E.V.Doroshenko, J.Matysik, S.de Vries, and H.J.de Groot (2008).
The associative nature of adenylyl transfer catalyzed by T4 DNA ligase.
  Proc Natl Acad Sci U S A, 105, 8563-8568.  
18238776 E.Cotner-Gohara, I.K.Kim, A.E.Tomkinson, and T.Ellenberger (2008).
Two DNA-binding and nick recognition modules in human DNA ligase III.
  J Biol Chem, 283, 10764-10772.  
18203718 H.Zhu, and S.Shuman (2008).
Bacterial nonhomologous end joining ligases preferentially seal breaks with a 3'-OH monoribonucleotide.
  J Biol Chem, 283, 8331-8339.  
18262407 J.M.Pascal (2008).
DNA and RNA ligases: structural variations and shared mechanisms.
  Curr Opin Struct Biol, 18, 96.  
18080330 N.Dwivedi, D.Dube, J.Pandey, B.Singh, V.Kukshal, R.Ramachandran, and R.P.Tripathi (2008).
NAD(+)-dependent DNA ligase: a novel target waiting for the right inhibitor.
  Med Res Rev, 28, 545-568.  
18782835 S.Jayaram, G.Ketner, N.Adachi, and L.A.Hanakahi (2008).
Loss of DNA ligase IV prevents recognition of DNA by double-strand break repair proteins XRCC4 and XLF.
  Nucleic Acids Res, 36, 5773-5786.  
18518823 T.Ellenberger, and A.E.Tomkinson (2008).
Eukaryotic DNA ligases: structural and functional insights.
  Annu Rev Biochem, 77, 313-338.  
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.  
17687496 H.Feng (2007).
Mutational analysis of bacterial NAD+-dependent DNA ligase: role of motif IV in ligation catalysis.
  Acta Biochim Biophys Sin (Shanghai), 39, 608-616.  
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
17585047 L.K.Wang, J.Nandakumar, B.Schwer, and S.Shuman (2007).
The C-terminal domain of T4 RNA ligase 1 confers specificity for tRNA repair.
  RNA, 13, 1235-1244.  
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
16420348 A.Zhao, F.C.Gray, and S.A.MacNeill (2006).
ATP- and NAD+-dependent DNA ligases share an essential function in the halophilic archaeon Haloferax volcanii.
  Mol Microbiol, 59, 743-752.  
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
16263720 K.El Omari, J.Ren, L.E.Bird, M.K.Bona, G.Klarmann, S.F.LeGrice, and D.K.Stammers (2006).
Molecular architecture and ligand recognition determinants for T4 RNA ligase.
  J Biol Chem, 281, 1573-1579.
PDB code: 2c5u
15987807 A.Martins, and S.Shuman (2005).
An end-healing enzyme from Clostridium thermocellum with 5' kinase, 2',3' phosphatase, and adenylyltransferase activities.
  RNA, 11, 1271-1280.  
15781861 G.Gao, A.M.Simpson, X.Kang, K.Rogers, M.Nebohacova, F.Li, and L.Simpson (2005).
Functional complementation of Trypanosoma brucei RNA in vitro editing with recombinant RNA ligase.
  Proc Natl Acad Sci U S A, 102, 4712-4717.  
15520014 H.Zhu, and S.Shuman (2005).
A primer-dependent polymerase function of pseudomonas aeruginosa ATP-dependent DNA ligase (LigD).
  J Biol Chem, 280, 418-427.  
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.  
15851476 J.Nandakumar, and S.Shuman (2005).
Dual mechanisms whereby a broken RNA end assists the catalysis of its repair by T4 RNA ligase 2.
  J Biol Chem, 280, 23484-23489.  
15691655 K.D.Stuart, A.Schnaufer, N.L.Ernst, and A.K.Panigrahi (2005).
Complex management: RNA editing in trypanosomes.
  Trends Biochem Sci, 30, 97.  
15923379 L.K.Wang, and S.Shuman (2005).
Structure-function analysis of yeast tRNA ligase.
  RNA, 11, 966-975.  
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.  
15611301 R.Sawaya, B.Schwer, and S.Shuman (2005).
Structure-function analysis of the yeast NAD+-dependent tRNA 2'-phosphotransferase Tpt1.
  RNA, 11, 107-113.  
14747466 A.Martins, and S.Shuman (2004).
Characterization of a baculovirus enzyme with RNA ligase, polynucleotide 5'-kinase, and polynucleotide 3'-phosphatase activities.
  J Biol Chem, 279, 18220-18231.  
15333634 A.Martins, and S.Shuman (2004).
An RNA ligase from Deinococcus radiodurans.
  J Biol Chem, 279, 50654-50661.  
14985346 C.Gong, A.Martins, P.Bongiorno, M.Glickman, and S.Shuman (2004).
Biochemical and genetic analysis of the four DNA ligases of mycobacteria.
  J Biol Chem, 279, 20594-20606.  
14962393 C.K.Ho, L.K.Wang, C.D.Lima, and S.Shuman (2004).
Structure and mechanism of RNA ligase.
  Structure, 12, 327-339.
PDB code: 1s68
15056675 H.Zhu, S.Yin, and S.Shuman (2004).
Characterization of polynucleotide kinase/phosphatase enzymes from Mycobacteriophages omega and Cjw1 and vibriophage KVP40.
  J Biol Chem, 279, 26358-26369.  
14752051 I.V.Martin, and S.A.MacNeill (2004).
Functional analysis of subcellular localization and protein-protein interaction sequences in the essential DNA ligase I protein of fission yeast.
  Nucleic Acids Res, 32, 632-642.  
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
15084599 J.Nandakumar, C.K.Ho, C.D.Lima, and S.Shuman (2004).
RNA substrate specificity and structure-guided mutational analysis of bacteriophage T4 RNA ligase 2.
  J Biol Chem, 279, 31337-31347.  
15494308 J.Nandakumar, and S.Shuman (2004).
How an RNA ligase discriminates RNA versus DNA damage.
  Mol Cell, 16, 211-221.  
15296738 K.S.Gajiwala, and C.Pinko (2004).
Structural rearrangement accompanying NAD+ synthesis within a bacterial DNA ligase crystal.
  Structure, 12, 1449-1459.
PDB codes: 1ta8 1tae
14730014 L.Simpson, R.Aphasizhev, G.Gao, and X.Kang (2004).
Mitochondrial proteins and complexes in Leishmania and Trypanosoma involved in U-insertion/deletion RNA editing.
  RNA, 10, 159-170.  
15328364 P.Liu, A.Burdzy, and L.C.Sowers (2004).
DNA ligases ensure fidelity by interrogating minor groove contacts.
  Nucleic Acids Res, 32, 4503-4511.  
15263063 P.S.Ng, and D.E.Bergstrom (2004).
Protein-DNA footprinting by endcapped duplex oligodeoxyribonucleotides.
  Nucleic Acids Res, 32, e107.  
15296724 S.Shuman (2004).
NAD+ specificity of bacterial DNA ligase revealed.
  Structure, 12, 1335-1336.  
14536071 A.Schnaufer, N.L.Ernst, S.S.Palazzo, J.O'Rear, R.Salavati, and K.Stuart (2003).
Separate insertion and deletion subcomplexes of the Trypanosoma brucei RNA editing complex.
  Mol Cell, 12, 307-319.  
12820968 C.Fabrega, V.Shen, S.Shuman, and C.D.Lima (2003).
Structure of an mRNA capping enzyme bound to the phosphorylated carboxy-terminal domain of RNA polymerase II.
  Mol Cell, 11, 1549-1561.
PDB code: 1p16
14602897 E.A.Worthey, A.Schnaufer, I.S.Mian, K.Stuart, and R.Salavati (2003).
Comparative analysis of editosome proteins in trypanosomatids.
  Nucleic Acids Res, 31, 6392-6408.  
12867414 H.Brötz-Oesterhelt, I.Knezevic, S.Bartel, T.Lampe, U.Warnecke-Eberz, K.Ziegelbauer, D.Häbich, and H.Labischinski (2003).
Specific and potent inhibition of NAD+-dependent DNA ligase by pyridochromanones.
  J Biol Chem, 278, 39435-39442.  
12682366 J.Smith, E.Riballo, B.Kysela, C.Baldeyron, K.Manolis, C.Masson, M.R.Lieber, D.Papadopoulo, and P.Jeggo (2003).
Impact of DNA ligase IV on the fidelity of end joining in human cells.
  Nucleic Acids Res, 31, 2157-2167.  
12519752 K.L.Carrick, and M.D.Topal (2003).
Amino acid substitutions at position 43 of NaeI endonuclease. Evidence for changes in NaeI structure.
  J Biol Chem, 278, 9733-9739.  
12766156 L.K.Wang, C.K.Ho, Y.Pei, and S.Shuman (2003).
Mutational analysis of bacteriophage T4 RNA ligase 1. Different functional groups are required for the nucleotidyl transfer and phosphodiester bond formation steps of the ligation reaction.
  J Biol Chem, 278, 29454-29462.  
12930960 M.Odell, L.Malinina, V.Sriskanda, M.Teplova, and S.Shuman (2003).
Analysis of the DNA joining repertoire of Chlorella virus DNA ligase and a new crystal structure of the ligase-adenylate intermediate.
  Nucleic Acids Res, 31, 5090-5100.
PDB code: 1p8l
12933796 R.Sawaya, B.Schwer, and S.Shuman (2003).
Genetic and biochemical analysis of the functional domains of yeast tRNA ligase.
  J Biol Chem, 278, 43928-43938.  
12611899 S.Yin, C.K.Ho, and S.Shuman (2003).
Structure-function analysis of T4 RNA ligase 2.
  J Biol Chem, 278, 17601-17608.  
12473094 A.V.Cherepanov, and S.de Vries (2002).
Dynamic mechanism of nick recognition by DNA ligase.
  Eur J Biochem, 269, 5993-5999.  
12228725 C.K.Ho, and S.Shuman (2002).
Bacteriophage T4 RNA ligase 2 (gp24.1) exemplifies a family of RNA ligases found in all phylogenetic domains.
  Proc Natl Acad Sci U S A, 99, 12709-12714.  
  11983065 I.V.Martin, and S.A.MacNeill (2002).
ATP-dependent DNA ligases.
  Genome Biol, 3, REVIEWS3005.  
11751916 V.Sriskanda, and S.Shuman (2002).
Role of nucleotidyl transferase motif V in strand joining by chlorella virus DNA ligase.
  J Biol Chem, 277, 9661-9667.  
11781321 V.Sriskanda, and S.Shuman (2002).
Conserved residues in domain Ia are required for the reaction of Escherichia coli DNA ligase with NAD+.
  J Biol Chem, 277, 9695-9700.  
11842101 V.Sriskanda, and S.Shuman (2002).
Role of nucleotidyltransferase motifs I, III and IV in the catalysis of phosphodiester bond formation by Chlorella virus DNA ligase.
  Nucleic Acids Res, 30, 903-911.  
11721015 A.V.Cherepanov, and S.de Vries (2001).
Binding of nucleotides by T4 DNA ligase and T4 RNA ligase: optical absorbance and fluorescence studies.
  Biophys J, 81, 3545-3559.  
11442824 A.Wilkinson, J.Day, and R.Bowater (2001).
Bacterial DNA ligases.
  Mol Microbiol, 40, 1241-1248.  
12762032 S.Shuman (2001).
The mRNA capping apparatus as drug target and guide to eukaryotic phylogeny.
  Cold Spring Harb Symp Quant Biol, 66, 301-312.  
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.