PDBsum entry: 1v9p

Ligase

PDB-id

1v9p


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Description

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Protein chains

Ligands

AMP ×2

Metal ions

_ZN ×2

Waters ×238

* Residue conservation analysis

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PDB id:

1v9p

Name:

Ligase

Title:

Crystal structure of NAD+-dependent DNA ligase

Structure:

DNA ligase. Chain: a, b. Synonym: polydeoxyribonucleotide synthase [nad+], tfi DNA ligase. Engineered: yes

Source:

Thermus filiformis. Organism_taxid: 276. Gene: liga. Expressed in: escherichia coli. Expression_system_taxid: 562

UniProt:

Chains A, B: Q9ZHI0 (DNLJ_THEFI)

Seq:

Struc:

Seq:

Struc:

Seq:

670 a.a.

Struc:

584 a.a.

Key:		PfamA domain
		Secondary structure			CATH domain

Enzyme class:

E.C.6.5.1.2 [IntEnz] [ExPASy] [KEGG] [BRENDA]

Reaction:

NAD⁺ + (deoxyribonucleotide)(n) + (deoxyribonucleotide)(m) = AMP + nicotinamide nucleotide + (deoxyribonucleotide)(n+m) (see diagram below)

Resolution:

2.90Å

R-factor:

0.232

R-free:

0.293

Authors:

J.Y.Lee,C.Chang,H.K.Song,J.Moon,J.K.Yang,H.K.Kim,S.K.Kwon, S.W.Suh

Key ref:

J.Y.Lee et al. (2000). Crystal structure of NAD(+)-dependent DNA ligase: modular architecture and functional implications.. EMBO J, 19, 1119-1129. [PubMed id: 10698952] [DOI: 10.1093/emboj/19.5.1119]

Date:

27-Jan-04

Release date:

30-Mar-04

Supersedes:

1dgt

Related entries:

1dgt
the previously deposited PDB coordinate(1dgt) had incorrect
portion because of imperfect amino acid sequence, which was
informed by other group. Therefore, we are going to replace
the old coordinate with the new one, which was modified
according to the correct amino acid sequence. Entry 1dgt is
obsoleted and superceded by this entry.

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Surface

Enzyme reaction for E.C.6.5.1.2

NAD(+)
Bound ligand (Het Group name = AMP)
matches with 50.00% similarity

{deoxyribonucleotide}(N)

{deoxyribonucleotide}(M)

AMP

nicotinamide nucleotide

{deoxyribonucleotide}(N+M)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site.

Key reference

DOI no: 10.1093/emboj/19.5.1119 EMBO J 19:1119-1129 (2000)

PubMed id: 10698952

Crystal structure of NAD(+)-dependent DNA ligase: modular architecture and functional implications.

J.Y.Lee, C.Chang, H.K.Song, J.Moon, J.K.Yang, H.K.Kim, S.T.Kwon, S.W.Suh.

ABSTRACT

DNA ligases catalyze the crucial step of joining the breaks in duplex DNA during DNA replication, repair and recombination, utilizing either ATP or NAD(+) as a cofactor. Despite the difference in cofactor specificity and limited overall sequence similarity, the two classes of DNA ligase share basically the same catalytic mechanism. In this study, the crystal structure of an NAD(+)-dependent DNA ligase from Thermus filiformis, a 667 residue multidomain protein, has been determined by the multiwavelength anomalous diffraction (MAD) method. It reveals highly modular architecture and a unique circular arrangement of its four distinct domains. It also provides clues for protein flexibility and DNA-binding sites. A model for the multidomain ligase action involving large conformational changes is proposed.

Selected figure(s)

Figure 2.
Figure 2 Stereo C[ ]superposition of Tfi DNA ligase. (A) One of the two crystallographically independent ligase molecules in the native structure takes a more closed conformation (gray) than the other (black), and its BRCT domain is visible in the electron density map. Superposition is made for domain 1. (B) Subdomain 1a of Bst ligase (gray) takes a very different orientation from that of Tfi ligase (black). Superposition is made for subdomain 1b. Figure 5.
Figure 5 Schematic model proposed for the Tfi ligase active site. Residues that are likely to participate in binding metal ions and the 5'-phosphate end of the nick are indicated.

The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2000, 19, 1119-1129) copyright 2000.

Figures were selected by an automated process.

Literature references that cite this PDB file's key reference

PubMed id Reference

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.

19502749 Y.Mizushina (2009).
Specific inhibitors of mammalian DNA polymerase species.

Biosci Biotechnol Biochem, 73, 1239-1251.

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.

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.

18511537 M.A.Brooks, L.Meslet-Cladiére, M.Graille, J.Kuhn, K.Blondeau, H.Myllykallio, and H.van Tilbeurgh (2008).
The structure of an archaeal homodimeric ligase which has RNA circularization activity.

Protein Sci, 17, 1336-1345.

PDB code: 2vug

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.

18065420 P.D.Robertson, E.M.Warren, H.Zhang, D.B.Friedman, J.W.Lary, J.L.Cole, A.V.Tutter, J.C.Walter, E.Fanning, and B.F.Eichman (2008).
Domain architecture and biochemical characterization of vertebrate mcm10.

J Biol Chem, 283, 3338-3348.

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.

17686784 C.Yuan, X.W.Lou, E.Rhoades, H.Chen, and L.A.Archer (2007).
T4 DNA ligase is more than an effective trap of cyclized dsDNA.

Nucleic Acids Res, 35, 5294-5302.

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.

18019526 H.Lin (2007).
Nicotinamide adenine dinucleotide: beyond a redox coenzyme.

Org Biomol Chem, 5, 2541-2554.

17488851 H.Zhu, and S.Shuman (2007).
Characterization of Agrobacterium tumefaciens DNA ligases C and D.

Nucleic Acids Res, 35, 3631-3645.

17426134 J.Y.Ha, H.K.Kim, d.o. .J.Kim, K.H.Kim, S.J.Oh, H.H.Lee, H.J.Yoon, H.K.Song, and S.W.Suh (2007).
The recombination-associated protein RdgC adopts a novel toroidal architecture for DNA binding.

Nucleic Acids Res, 35, 2671-2681.

PDB code: 2owy

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.

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

17094803 D.C.Zappulla, A.S.Maharaj, J.J.Connelly, R.A.Jockusch, and R.Sternglanz (2006).
Rtt107/Esc4 binds silent chromatin and DNA repair proteins using different BRCT motifs.

BMC Mol Biol, 7, 40.

17132163 L.Poidevin, and S.A.MacNeill (2006).
Biochemical characterisation of LigN, an NAD+-dependent DNA ligase from the halophilic euryarchaeon Haloferax volcanii that displays maximal in vitro activity at high salt concentrations.

BMC Mol Biol, 7, 44.

16361700 M.Kobayashi, F.Figaroa, N.Meeuwenoord, L.E.Jansen, and G.Siegal (2006).
Characterization of the DNA binding and structural properties of the BRCT region of human replication factor C p140 subunit.

J Biol Chem, 281, 4308-4317.

16483311 T.Takeuchi, T.Ishidoh, H.Iijima, I.Kuriyama, N.Shimazaki, O.Koiwai, K.Kuramochi, S.Kobayashi, F.Sugawara, K.Sakaguchi, H.Yoshida, and Y.Mizushina (2006).
Structural relationship of curcumin derivatives binding to the BRCT domain of human DNA polymerase lambda.

Genes Cells, 11, 223-235.

15724163 G.Zauner, Y.Wang, M.Lavesa-Curto, A.MacDonald, A.G.Mayes, R.P.Bowater, and J.N.Butt (2005).
Tethered DNA hairpins facilitate electrochemical detection of DNA ligation.

Analyst, 130, 345-349.

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.

15724164 L.Liu, Z.Tang, K.Wang, W.Tan, J.Li, Q.Guo, X.Meng, and C.Ma (2005).
Using molecular beacon to monitor activity of E. coli DNA ligase.

Analyst, 130, 350-357.

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

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.

15116069 B.I.Lee, K.H.Kim, S.J.Park, S.H.Eom, H.K.Song, and S.W.Suh (2004).
Ring-shaped architecture of RecR: implications for its role in homologous recombinational DNA repair.

EMBO J, 23, 2029-2038.

PDB code: 1vdd

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.

14747344 D.Georlette, V.Blaise, F.Bouillenne, B.Damien, S.H.Thorbjarnardóttir, E.Depiereux, C.Gerday, V.N.Uversky, and G.Feller (2004).
Adenylation-dependent conformation and unfolding pathways of the NAD+-dependent DNA ligase from the thermophile Thermus scotoductus.

Biophys J, 86, 1089-1104.

15268945 H.J.Jeon, H.J.Shin, J.J.Choi, H.S.Hoe, H.K.Kim, S.W.Suh, and S.T.Kwon (2004).
Mutational analyses of the thermostable NAD+-dependent DNA ligase from Thermus filiformis.

FEMS Microbiol Lett, 237, 111-118.

15037606 I.Bougie, and M.Bisaillon (2004).
The broad spectrum antiviral nucleoside ribavirin as a substrate for a viral RNA capping enzyme.

J Biol Chem, 279, 22124-22130.

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.

15090549 M.E.Stauffer, and W.J.Chazin (2004).
Structural mechanisms of DNA replication, repair, and recombination.

J Biol Chem, 279, 30915-30918.

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.

12857762 D.Georlette, B.Damien, V.Blaise, E.Depiereux, V.N.Uversky, C.Gerday, and G.Feller (2003).
Structural and functional adaptations to extreme temperatures in psychrophilic, mesophilic, and thermophilic DNA ligases.

J Biol Chem, 278, 37015-37023.

14523019 D.Georlette, V.Blaise, C.Dohmen, F.Bouillenne, B.Damien, E.Depiereux, C.Gerday, V.N.Uversky, and G.Feller (2003).
Cofactor binding modulates the conformational stabilities and unfolding patterns of NAD(+)-dependent DNA ligases from Escherichia coli and Thermus scotoductus.

J Biol Chem, 278, 49945-49953.

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.

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.

12527760 S.S.Krishna, I.Majumdar, and N.V.Grishin (2003).
Structural classification of zinc fingers: survey and summary.

Nucleic Acids Res, 31, 532-550.

12611899 S.Yin, C.K.Ho, and S.Shuman (2003).
Structure-function analysis of T4 RNA ligase 2.

J Biol Chem, 278, 17601-17608.

14654700 T.Blondal, S.H.Hjorleifsdottir, O.F.Fridjonsson, A.Aevarsson, S.Skirnisdottir, A.G.Hermannsdottir, G.O.Hreggvidsson, A.V.Smith, and J.K.Kristjansson (2003).
Discovery and characterization of a thermostable bacteriophage RNA ligase homologous to T4 RNA ligase 1.

Nucleic Acids Res, 31, 7247-7254.

12651953 Y.Liu, J.Zhou, M.V.Omelchenko, A.S.Beliaev, A.Venkateswaran, J.Stair, L.Wu, D.K.Thompson, D.Xu, I.B.Rogozin, E.K.Gaidamakova, M.Zhai, K.S.Makarova, E.V.Koonin, and M.J.Daly (2003).
Transcriptome dynamics of Deinococcus radiodurans recovering from ionizing radiation.

Proc Natl Acad Sci U S A, 100, 4191-4196.

12473094 A.V.Cherepanov, and S.de Vries (2002).
Dynamic mechanism of nick recognition by DNA ligase.

Eur J Biochem, 269, 5993-5999.

12207707 C.A.Blindauer, M.D.Harrison, A.K.Robinson, J.A.Parkinson, P.W.Bowness, P.J.Sadler, and N.J.Robinson (2002).
Multiple bacteria encode metallothioneins and SmtA-like zinc fingers.

Mol Microbiol, 45, 1421-1432.

12426397 S.Singh, G.E.Folkers, A.M.Bonvin, R.Boelens, R.Wechselberger, A.Niztayev, and R.Kaptein (2002).
Solution structure and DNA-binding properties of the C-terminal domain of UvrC from E.coli.

EMBO J, 21, 6257-6266.

PDB code: 1kft

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.

11325928 F.S.Kaczmarek, R.P.Zaniewski, T.D.Gootz, D.E.Danley, M.N.Mansour, M.Griffor, A.V.Kamath, M.Cronan, J.Mueller, D.Sun, P.K.Martin, B.Benton, L.McDowell, D.Biek, and M.B.Schmid (2001).
Cloning and functional characterization of an NAD(+)-dependent DNA ligase from Staphylococcus aureus.

J Bacteriol, 183, 3016-3024.

11573079 R.Baer (2001).
With the ends in sight: images from the BRCA1 tumor suppressor.

Nat Struct Biol, 8, 822-824.

11573086 R.S.Williams, R.Green, and J.N.Glover (2001).
Crystal structure of the BRCT repeat region from the breast cancer-associated protein BRCA1.

Nat Struct Biol, 8, 838-842.

PDB code: 1jnx

11812821 V.Sriskanda, and S.Shuman (2001).
A second NAD(+)-dependent DNA ligase (LigB) in Escherichia coli.

Nucleic Acids Res, 29, 4930-4934.

11058099 A.J.Doherty, and S.W.Suh (2000).
Structural and mechanistic conservation in DNA ligases.

Nucleic Acids Res, 28, 4051-4058.

11095673 M.A.Petit, and S.D.Ehrlich (2000).
The NAD-dependent ligase encoded by yerG is an essential gene of Bacillus subtilis.

Nucleic Acids Res, 28, 4642-4648.

11040219 T.F.Mah, K.Kuznedelov, A.Mushegian, K.Severinov, and J.Greenblatt (2000).
The alpha subunit of E. coli RNA polymerase activates RNA binding by NusA.

Genes Dev, 14, 2664-2675.

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.