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PDBsum entry 1k4t

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protein dna_rna ligands metals links
Isomerase/DNA PDB id
1k4t
Jmol
Contents
Protein chain
565 a.a. *
DNA/RNA
Ligands
TTG
TTC
PG4
Metals
_HG
Waters ×227
* Residue conservation analysis
PDB id:
1k4t
Name: Isomerase/DNA
Title: Human DNA topoisomerase i (70 kda) in complex with the poison topotecan and covalent complex with a 22 base pair DNA duplex
Structure: 5'-d( Ap Ap Ap Ap Ap Gp Ap Cp Tp T)-3'. Chain: b. Engineered: yes. 5'-d( (Tgp)p Gp Ap Ap Ap Ap Ap Tp Tp Tp Tp T)-3'. Chain: c. Engineered: yes. 5'- d( Ap Ap Ap Ap Ap Tp Tp Tp Tp Tp Cp Cp Ap Ap Gp Tp Cp Tp Tp Tp Tp T)-3'.
Source: Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
Biol. unit: Tetramer (from PQS)
Resolution:
2.10Å     R-factor:   0.229     R-free:   0.269
Authors: B.L.Staker,K.Hjerrild,M.D.Feese,C.A.Behnke,A.B.Burgin Jr., L.J.Stewart
Key ref:
B.L.Staker et al. (2002). The mechanism of topoisomerase I poisoning by a camptothecin analog. Proc Natl Acad Sci U S A, 99, 15387-15392. PubMed id: 12426403 DOI: 10.1073/pnas.242259599
Date:
08-Oct-01     Release date:   04-Dec-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P11387  (TOP1_HUMAN) -  DNA topoisomerase 1
Seq:
Struc:
 
Seq:
Struc:
765 a.a.
565 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.5.99.1.2  - Dna topoisomerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP-independent breakage of single-stranded DNA, followed by passage and rejoining.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     chromosome   1 term 
  Biological process     DNA topological change   1 term 
  Biochemical function     DNA binding     3 terms  

 

 
DOI no: 10.1073/pnas.242259599 Proc Natl Acad Sci U S A 99:15387-15392 (2002)
PubMed id: 12426403  
 
 
The mechanism of topoisomerase I poisoning by a camptothecin analog.
B.L.Staker, K.Hjerrild, M.D.Feese, C.A.Behnke, A.B.Burgin, L.Stewart.
 
  ABSTRACT  
 
We report the x-ray crystal structure of human topoisomerase I covalently joined to double-stranded DNA and bound to the clinically approved anticancer agent Topotecan. Topotecan mimics a DNA base pair and binds at the site of DNA cleavage by intercalating between the upstream (-1) and downstream (+1) base pairs. Intercalation displaces the downstream DNA, thus preventing religation of the cleaved strand. By specifically binding to the enzyme-substrate complex, Topotecan acts as an uncompetitive inhibitor. The structure can explain several of the known structure-activity relationships of the camptothecin family of anticancer drugs and suggests that there are at least two classes of mutations that can produce a drug-resistant enzyme. The first class includes changes to residues that contribute to direct interactions with the drug, whereas a second class would alter interactions with the DNA and thereby destabilize the drug-binding site.
 
  Selected figure(s)  
 
Figure 2.
Fig 2. Topotecan electron density. (A) Topotecan with reversible hydrolysis of the E-ring from the closed lactone form to the open carboxylate form is diagrammed. (B) A 3.0 ||Fo||-||Fc|| omit map of electron density for Topotecan is illustrated. (C) A 3.0 ||Fo||-||Fc|| electron density map calculated with the lactone form of Topotecan (100% closed E-ring) is diagrammed. Negative electron density (red) is seen in the vicinity of the lactone oxygen, and positive (blue) electron density peaks are located nearby. (D) A 3.0 ||Fo||-||Fc|| electron density calculated with the carboxylate form of Topotecan (100% open E-ring) is diagrammed. Negative electron density (red) surrounds the terminal hydroxyl and carboxylic acid moieties, whereas a positive (blue) electron density peak is in the location of what would be the lactone oxygen in the closed E-ring conformation.
Figure 3.
Fig 3. Stereoview of Topotecan binding. The Topotecan interactions with protein side chains for the lactone (A, blue) and carboxylate (B, gold) forms of the drug are depicted. Hydrogen bonds (predicted by contact distance and geometry of the refined atomic positions) are shown as solid blue lines, and the calculated interatomic distances are indicated. Labels for residues that result in resistance to CPT when mutated are highlighted in yellow. The oxygen atoms of water molecules are depicted as light blue spheres. Protein side chains are green, and noncarbon atoms are colored red for oxygen, blue for nitrogen, and magenta for phosphorus. The DNA and protein side chains that do not interact with Topotecan have been omitted from the figure.
 
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22173432 Y.Pommier, and C.Marchand (2012).
Interfacial inhibitors: targeting macromolecular complexes.
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22108601 S.M.Vos, E.M.Tretter, B.H.Schmidt, and J.M.Berger (2011).
All tangled up: how cells direct, manage and exploit topoisomerase function.
  Nat Rev Mol Cell Biol, 12, 827-841.  
20485741 B.A.Neto, A.A.Lapis, F.S.Mancilha, E.L.Batista, P.A.Netz, F.Rominger, L.A.Basso, D.S.Santos, and J.Dupont (2010).
On the selective detection of duplex deoxyribonucleic acids by 2,1,3-benzothiadiazole fluorophores.
  Mol Biosyst, 6, 967-975.  
21069656 C.Samorì, G.L.Beretta, G.Varchi, A.Guerrini, S.Di Micco, S.Basili, G.Bifulco, R.Riccio, S.Moro, E.Bombardelli, F.Zunino, and G.Fontana (2010).
Structure-activity relationship study of 16‚ÄČa-thiocamptothecins: an integrated in vitro and in silico approach.
  ChemMedChem, 5, 2006-2015.  
19883377 C.Tesauro, P.Fiorani, I.D'Annessa, G.Chillemi, G.Turchi, and A.Desideri (2010).
Erybraedin C, a natural compound from the plant Bituminaria bituminosa, inhibits both the cleavage and religation activities of human topoisomerase I.
  Biochem J, 425, 531-539.  
20723754 D.A.Koster, A.Crut, S.Shuman, M.A.Bjornsti, and N.H.Dekker (2010).
Cellular strategies for regulating DNA supercoiling: a single-molecule perspective.
  Cell, 142, 519-530.  
20565729 H.P.Tsai, L.W.Lin, Z.Y.Lai, J.Y.Wu, C.E.Chen, J.Hwang, C.S.Chen, and C.M.Lin (2010).
Immobilizing topoisomerase I on a surface plasmon resonance biosensor chip to screen for inhibitors.
  J Biomed Sci, 17, 49.  
21077066 J.Guo, G.Chen, X.Ning, M.A.Wolfert, X.Li, B.Xu, and G.J.Boons (2010).
Surface modification of polymeric micelles by strain-promoted alkyne-azide cycloadditions.
  Chemistry, 16, 13360-13366.  
20624816 J.Lipfert, S.Klijnhout, and N.H.Dekker (2010).
Torsional sensing of small-molecule binding using magnetic tweezers.
  Nucleic Acids Res, 38, 7122-7132.  
20068096 S.M.Arnold, J.J.Rinehart, E.Tsakalozou, J.R.Eckardt, S.Z.Fields, B.J.Shelton, P.A.DeSimone, B.K.Kee, J.A.Moscow, and M.Leggas (2010).
A phase I study of 7-t-butyldimethylsilyl-10-hydroxycamptothecin in adult patients with refractory or metastatic solid malignancies.
  Clin Cancer Res, 16, 673-680.  
20947527 T.Cheng, Y.Wang, and S.H.Bryant (2010).
Investigating the correlations among the chemical structures, bioactivity profiles and molecular targets of small molecules.
  Bioinformatics, 26, 2881-2888.  
20603643 T.H.Huang, H.C.Chen, S.M.Chou, Y.C.Yang, J.R.Fan, and T.K.Li (2010).
Cellular processing determinants for the activation of damage signals in response to topoisomerase I-linked DNA breakage.
  Cell Res, 20, 1060-1075.  
20534341 Y.Pommier, E.Leo, H.Zhang, and C.Marchand (2010).
DNA topoisomerases and their poisoning by anticancer and antibacterial drugs.
  Chem Biol, 17, 421-433.  
20155916 Y.Song, Z.Shao, T.S.Dexheimer, E.S.Scher, Y.Pommier, and M.Cushman (2010).
Structure-based design, synthesis, and biological studies of new anticancer norindenoisoquinoline topoisomerase I inhibitors.
  J Med Chem, 53, 1979-1989.  
19332675 A.Roy, S.BoseDasgupta, A.Ganguly, P.Jaisankar, and H.K.Majumder (2009).
Topoisomerase I gene mutations at F270 in the large subunit and N184 in the small subunit contribute to the resistance mechanism of the unicellular parasite Leishmania donovani towards 3,3'-diindolylmethane.
  Antimicrob Agents Chemother, 53, 2589-2598.  
19472416 C.Punchihewa, M.Carver, and D.Yang (2009).
DNA sequence selectivity of human topoisomerase I-mediated DNA cleavage induced by camptothecin.
  Protein Sci, 18, 1326-1331.  
19291733 D.Pla, A.Sischka, F.Albericio, M.Alvarez, X.Fernàndez-Busquets, and D.Anselmetti (2009).
Optical tweezers study of topoisomerase inhibition.
  Small, 5, 1269-1272.  
19720733 I.Dalla Rosa, S.Goffart, M.Wurm, C.Wiek, F.Essmann, S.Sobek, P.Schroeder, H.Zhang, J.Krutmann, H.Hanenberg, K.Schulze-Osthoff, C.Mielke, Y.Pommier, F.Boege, and M.O.Christensen (2009).
Adaptation of topoisomerase I paralogs to nuclear and mitochondrial DNA.
  Nucleic Acids Res, 37, 6414-6428.  
19377506 J.L.Nitiss (2009).
Targeting DNA topoisomerase II in cancer chemotherapy.
  Nat Rev Cancer, 9, 338-350.  
19277971 K.E.Hubbard, P.Schaiquevich, F.Bai, C.H.Fraga, L.Miller, J.C.Panetta, and C.F.Stewart (2009).
Application of a highly specific and sensitive fluorescent HPLC method for topotecan lactone in whole blood.
  Biomed Chromatogr, 23, 707-713.  
19424733 K.G.Byler, C.Wang, and W.N.Setzer (2009).
Quinoline alkaloids as intercalative topoisomerase inhibitors.
  J Mol Model, 15, 1417-1426.  
19783447 M.A.Cinelli, B.Cordero, T.S.Dexheimer, Y.Pommier, and M.Cushman (2009).
Synthesis and biological evaluation of 14-(aminoalkyl-aminomethyl)aromathecins as topoisomerase I inhibitors: investigating the hypothesis of shared structure-activity relationships.
  Bioorg Med Chem, 17, 7145-7155.  
19106140 N.M.Baker, R.Rajan, and A.Mondragón (2009).
Structural studies of type I topoisomerases.
  Nucleic Acids Res, 37, 693-701.  
19767617 P.Fiorani, C.Tesauro, G.Mancini, G.Chillemi, I.D'Annessa, G.Graziani, L.Tentori, A.Muzi, and A.Desideri (2009).
Evidence of the crucial role of the linker domain on the catalytic activity of human topoisomerase I by experimental and simulative characterization of the Lys681Ala mutant.
  Nucleic Acids Res, 37, 6849-6858.  
19561619 S.Renner, W.A.van Otterlo, M.Dominguez Seoane, S.Möcklinghoff, B.Hofmann, S.Wetzel, A.Schuffenhauer, P.Ertl, T.I.Oprea, D.Steinhilber, L.Brunsveld, D.Rauh, and H.Waldmann (2009).
Bioactivity-guided mapping and navigation of chemical space.
  Nat Chem Biol, 5, 585-592.  
19383846 Y.Pommier, and M.Cushman (2009).
The indenoisoquinoline noncamptothecin topoisomerase I inhibitors: update and perspectives.
  Mol Cancer Ther, 8, 1008-1014.  
19476377 Y.Pommier (2009).
DNA topoisomerase I inhibitors: chemistry, biology, and interfacial inhibition.
  Chem Rev, 109, 2894-2902.  
18755053 A.J.Schoeffler, and J.M.Berger (2008).
DNA topoisomerases: harnessing and constraining energy to govern chromosome topology.
  Q Rev Biophys, 41, 41.  
18772225 C.Losasso, E.Cretaio, P.Fiorani, I.D'Annessa, G.Chillemi, and P.Benedetti (2008).
A single mutation in the 729 residue modulates human DNA topoisomerase IB DNA binding and drug resistance.
  Nucleic Acids Res, 36, 5635-5644.  
18292117 D.A.Koster, F.Czerwinski, L.Halby, A.Crut, P.Vekhoff, K.Palle, P.B.Arimondo, and N.H.Dekker (2008).
Single-molecule observations of topotecan-mediated TopIB activity at a unique DNA sequence.
  Nucleic Acids Res, 36, 2301-2310.  
18765473 G.Chillemi, I.D'Annessa, P.Fiorani, C.Losasso, P.Benedetti, and A.Desideri (2008).
Thr729 in human topoisomerase I modulates anti-cancer drug resistance by altering protein domain communications as suggested by molecular dynamics simulations.
  Nucleic Acids Res, 36, 5645-5651.  
18215123 G.S.Laco, and Y.Pommier (2008).
Role of a tryptophan anchor in human topoisomerase I structure, function and inhibition.
  Biochem J, 411, 523-530.  
18508107 H.Kim, J.H.Cardellina, R.Akee, J.J.Champoux, and J.T.Stivers (2008).
Arylstibonic acids: novel inhibitors and activators of human topoisomerase IB.
  Bioorg Chem, 36, 190-197.  
18318502 J.E.Deweese, A.B.Burgin, and N.Osheroff (2008).
Using 3'-bridging phosphorothiolates to isolate the forward DNA cleavage reaction of human topoisomerase IIalpha.
  Biochemistry, 47, 4129-4140.  
18693244 K.Palle, L.Pattarello, M.van der Merwe, C.Losasso, P.Benedetti, and M.A.Bjornsti (2008).
Disulfide cross-links reveal conserved features of DNA topoisomerase I architecture and a role for the N terminus in clamp closure.
  J Biol Chem, 283, 27767-27775.  
18630891 M.A.Cinelli, A.Morrell, T.S.Dexheimer, E.S.Scher, Y.Pommier, and M.Cushman (2008).
Design, synthesis, and biological evaluation of 14-substituted aromathecins as topoisomerase I inhibitors.
  J Med Chem, 51, 4609-4619.  
18805512 M.Christmann, M.T.Tomicic, C.Gestrich, W.P.Roos, V.A.Bohr, and B.Kaina (2008).
WRN protects against topo I but not topo II inhibitors by preventing DNA break formation.
  DNA Repair (Amst), 7, 1999-2009.  
18443285 S.Sirikantaramas, M.Yamazaki, and K.Saito (2008).
Mutations in topoisomerase I as a self-resistance mechanism coevolved with the production of the anticancer alkaloid camptothecin in plants.
  Proc Natl Acad Sci U S A, 105, 6782-6786.  
18630893 S.Zhong, X.Chen, X.Zhu, B.Dziegielewska, K.E.Bachman, T.Ellenberger, J.D.Ballin, G.M.Wilson, A.E.Tomkinson, and A.D.MacKerell (2008).
Identification and validation of human DNA ligase inhibitors using computer-aided drug design.
  J Med Chem, 51, 4553-4562.  
18927559 T.S.Dexheimer, and Y.Pommier (2008).
DNA cleavage assay for the identification of topoisomerase I inhibitors.
  Nat Protoc, 3, 1736-1750.  
18451142 X.Chen, S.Zhong, X.Zhu, B.Dziegielewska, T.Ellenberger, G.M.Wilson, A.D.MacKerell, and A.E.Tomkinson (2008).
Rational design of human DNA ligase inhibitors that target cellular DNA replication and repair.
  Cancer Res, 68, 3169-3177.  
18636761 Y.Song, and M.Cushman (2008).
The binding orientation of a norindenoisoquinoline in the topoisomerase I-DNA cleavage complex is primarily governed by pi-pi stacking interactions.
  J Phys Chem B, 112, 9484-9489.  
17241535 A.J.Lu, Z.S.Zhang, M.Y.Zheng, H.J.Zou, X.M.Luo, and H.L.Jiang (2007).
3D-QSAR study of 20 (S)-camptothecin analogs.
  Acta Pharmacol Sin, 28, 307-314.  
17072654 A.Lauria, M.Ippolito, and A.M.Almerico (2007).
Molecular docking approach on the Topoisomerase I inhibitors series included in the NCI anti-cancer agents mechanism database.
  J Mol Model, 13, 393-400.  
17434318 C.Punchihewa, J.Dai, M.Carver, and D.Yang (2007).
Human topoisomerase I C-terminal domain fragment containing the active site tyrosine is a molten globule: implication for the formation of competent productive complex.
  J Struct Biol, 159, 111-121.  
17589503 D.A.Koster, K.Palle, E.S.Bot, M.A.Bjornsti, and N.H.Dekker (2007).
Antitumour drugs impede DNA uncoiling by topoisomerase I.
  Nature, 448, 213-217.  
17439970 G.Chillemi, A.Bruselles, P.Fiorani, S.Bueno, and A.Desideri (2007).
The open state of human topoisomerase I as probed by molecular dynamics simulation.
  Nucleic Acids Res, 35, 3032-3038.  
18254239 I.Choi, C.Kim, and S.Choi (2007).
Binding mode analysis of topoisomerase inhibitors, 6-arylamino-7-chloro-quinazoline-5,8-diones, within the cleavable complex of human topoisomerase I and DNA.
  Arch Pharm Res, 30, 1526-1535.  
17885736 J.Chen, Q.Lu, and J.P.Balthasar (2007).
Mathematical modeling of topotecan pharmacokinetics and toxicodynamics in mice.
  J Pharmacokinet Pharmacodyn, 34, 829-847.  
17024403 N.R.Jena, and P.C.Mishra (2007).
A theoretical study of some new analogues of the anti-cancer drug camptothecin.
  J Mol Model, 13, 267-274.  
16841091 N.Sen, B.Banerjee, B.B.Das, A.Ganguly, T.Sen, S.Pramanik, S.Mukhopadhyay, and H.K.Majumder (2007).
Apoptosis is induced in leishmanial cells by a novel protein kinase inhibitor withaferin A and is facilitated by apoptotic topoisomerase I-DNA complex.
  Cell Death Differ, 14, 358-367.  
17095016 Q.A.Khan, and D.S.Pilch (2007).
Topoisomerase I-mediated DNA cleavage induced by the minor groove-directed binding of bibenzimidazoles to a distal site.
  J Mol Biol, 365, 561-569.  
17827209 R.F.Frøhlich, C.Veigaard, F.F.Andersen, A.K.McClendon, A.C.Gentry, A.H.Andersen, N.Osheroff, T.Stevnsner, and B.R.Knudsen (2007).
Tryptophane-205 of human topoisomerase I is essential for camptothecin inhibition of negative but not positive supercoil removal.
  Nucleic Acids Res, 35, 6170-6180.  
17181156 A.Morrell, S.Antony, G.Kohlhagen, Y.Pommier, and M.Cushman (2006).
A systematic study of nitrated indenoisoquinolines reveals a potent topoisomerase I inhibitor.
  J Med Chem, 49, 7740-7753.  
16488884 B.B.Das, N.Sen, A.Roy, S.B.Dasgupta, A.Ganguly, B.C.Mohanta, B.Dinda, and H.K.Majumder (2006).
Differential induction of Leishmania donovani bi-subunit topoisomerase I-DNA cleavage complex by selected flavones and camptothecin: activity of flavones against camptothecin-resistant topoisomerase I.
  Nucleic Acids Res, 34, 1121-1132.  
17042788 B.B.Das, T.Sengupta, A.Ganguly, and H.K.Majumder (2006).
Topoisomerases of kinetoplastid parasites: why so fascinating?
  Mol Microbiol, 62, 917-927.  
16505102 C.Marchand, S.Antony, K.W.Kohn, M.Cushman, A.Ioanoviciu, B.L.Staker, A.B.Burgin, L.Stewart, and Y.Pommier (2006).
A novel norindenoisoquinoline structure reveals a common interfacial inhibitor paradigm for ternary trapping of the topoisomerase I-DNA covalent complex.
  Mol Cancer Ther, 5, 287-295.  
16996084 D.F.Fujimoto, C.Pinilla, and A.M.Segall (2006).
New peptide inhibitors of type IB topoisomerases: similarities and differences vis-a-vis inhibitors of tyrosine recombinases.
  J Mol Biol, 363, 891-907.  
16151810 D.J.Adams, M.W.da Silva, J.L.Flowers, G.Kohlhagen, Y.Pommier, O.M.Colvin, G.Manikumar, and M.C.Wani (2006).
Camptothecin analogs with enhanced activity against human breast cancer cells. I. Correlation of potency with lipophilicity and persistence in the cleavage complex.
  Cancer Chemother Pharmacol, 57, 135-144.  
16819197 K.Bielawski, K.Winnicka, and A.Bielawska (2006).
Inhibition of DNA topoisomerases I and II, and growth inhibition of breast cancer MCF-7 cells by ouabain, digoxin and proscillaridin A.
  Biol Pharm Bull, 29, 1493-1497.  
16885024 K.Perry, Y.Hwang, F.D.Bushman, and G.D.Van Duyne (2006).
Structural basis for specificity in the poxvirus topoisomerase.
  Mol Cell, 23, 343-354.
PDB codes: 2h7f 2h7g
17034134 M.Nagarajan, A.Morrell, A.Ioanoviciu, S.Antony, G.Kohlhagen, K.Agama, M.Hollingshead, Y.Pommier, and M.Cushman (2006).
Synthesis and evaluation of indenoisoquinoline topoisomerase I inhibitors substituted with nitrogen heterocycles.
  J Med Chem, 49, 6283-6289.  
16990249 P.Fiorani, G.Chillemi, C.Losasso, S.Castelli, and A.Desideri (2006).
The different cleavage DNA sequence specificity explains the camptothecin resistance of the human topoisomerase I Glu418Lys mutant.
  Nucleic Acids Res, 34, 5093-5100.  
16846801 R.Balaña-Fouce, C.M.Redondo, Y.Pérez-Pertejo, R.Díaz-González, and R.M.Reguera (2006).
Targeting atypical trypanosomatid DNA topoisomerase I.
  Drug Discov Today, 11, 733-740.  
16480276 X.Xiao, S.Antony, Y.Pommier, and M.Cushman (2006).
Total synthesis and biological evaluation of 22-hydroxyacuminatine.
  J Med Chem, 49, 1408-1412.  
16990856 Y.Pommier (2006).
Topoisomerase I inhibitors: camptothecins and beyond.
  Nat Rev Cancer, 6, 789-802.  
16891172 Y.Pommier, J.M.Barcelo, V.A.Rao, O.Sordet, A.G.Jobson, L.Thibaut, Z.H.Miao, J.A.Seiler, H.Zhang, C.Marchand, K.Agama, J.L.Nitiss, and C.Redon (2006).
Repair of topoisomerase I-mediated DNA damage.
  Prog Nucleic Acid Res Mol Biol, 81, 179-229.  
15944452 G.Chillemi, P.Fiorani, S.Castelli, A.Bruselles, P.Benedetti, and A.Desideri (2005).
Effect on DNA relaxation of the single Thr718Ala mutation in human topoisomerase I: a functional and molecular dynamics study.
  Nucleic Acids Res, 33, 3339-3350.  
15920477 H.Interthal, H.J.Chen, T.E.Kehl-Fie, J.Zotzmann, J.B.Leppard, and J.J.Champoux (2005).
SCAN1 mutant Tdp1 accumulates the enzyme--DNA intermediate and causes camptothecin hypersensitivity.
  EMBO J, 24, 2224-2233.  
15830206 J.B.Leppard, and J.J.Champoux (2005).
Human DNA topoisomerase I: relaxation, roles, and damage control.
  Chromosoma, 114, 75-85.  
16207129 K.Durand-Faucher, H.Rabinovitch-Chable, H.Dzugan, S.Charret, K.Aubry, D.Genet, S.Léobon, N.Tubiana-Mathieu, J.Cook-Moreau, M.Rigaud, and F.G.Sturtz (2005).
A quantitative RT-PCR method to determine topoisomerase I mRNA levels in human tissue samples.
  Clin Chem Lab Med, 43, 707-714.  
16314322 L.Sari, and I.Andricioaei (2005).
Rotation of DNA around intact strand in human topoisomerase I implies distinct mechanisms for positive and negative supercoil relaxation.
  Nucleic Acids Res, 33, 6621-6634.  
15837190 L.Tian, C.D.Claeboe, S.M.Hecht, and S.Shuman (2005).
Mechanistic plasticity of DNA topoisomerase IB: phosphate electrostatics dictate the need for a catalytic arginine.
  Structure, 13, 513-520.  
15959561 M.Malanga, and F.R.Althaus (2005).
The role of poly(ADP-ribose) in the DNA damage signaling network.
  Biochem Cell Biol, 83, 354-364.  
15670945 N.J.Rahier, B.M.Eisenhauer, R.Gao, S.J.Thomas, and S.M.Hecht (2005).
On the role of E-ring oxygen atoms in the binding of camptothecin to the topoisomerase I-DNA covalent binary complex.
  Bioorg Med Chem, 13, 1381-1386.  
16011334 X.Xiao, and M.Cushman (2005).
An ab initio quantum mechanics calculation that correlates with ligand orientation and DNA cleavage site selectivity in camptothecin-DNA-topoisomerase I ternary cleavage complexes.
  J Am Chem Soc, 127, 9960-9961.  
15749159 Y.Pommier, and J.Cherfils (2005).
Interfacial inhibition of macromolecular interactions: nature's paradigm for drug discovery.
  Trends Pharmacol Sci, 26, 138-145.  
15347588 G.Chillemi, M.Redinbo, A.Bruselles, and A.Desideri (2004).
Role of the linker domain and the 203-214 N-terminal residues in the human topoisomerase I DNA complex dynamics.
  Biophys J, 87, 4087-4097.  
15494452 J.J.Vermeersch, S.Christmann-Franck, L.V.Karabashyan, S.Fermandjian, G.Mirambeau, and P.A.Der Garabedian (2004).
Pyridoxal 5'-phosphate inactivates DNA topoisomerase IB by modifying the lysine general acid.
  Nucleic Acids Res, 32, 5649-5657.  
15139806 K.D.Corbett, and J.M.Berger (2004).
Structure, molecular mechanisms, and evolutionary relationships in DNA topoisomerases.
  Annu Rev Biophys Biomol Struct, 33, 95.  
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Enhancement of camptothecin-induced topoisomerase I cleavage complexes by the acetaldehyde adduct N2-ethyl-2'-deoxyguanosine.
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Human topoisomerase I poisoning: docking protoberberines into a structure-based binding site model.
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12810956 A.L.Bodley, A.K.Chakraborty, S.Xie, C.Burri, and T.A.Shapiro (2003).
An unusual type IB topoisomerase from African trypanosomes.
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12595561 G.Chillemi, P.Fiorani, P.Benedetti, and A.Desideri (2003).
Protein concerted motions in the DNA-human topoisomerase I complex.
  Nucleic Acids Res, 31, 1525-1535.  
14527324 G.L.Verdine, and D.P.Norman (2003).
Covalent trapping of protein-DNA complexes.
  Annu Rev Biochem, 72, 337-366.  
12887905 L.Tian, C.D.Claeboe, S.M.Hecht, and S.Shuman (2003).
Guarding the genome: electrostatic repulsion of water by DNA suppresses a potent nuclease activity of topoisomerase IB.
  Mol Cell, 12, 199-208.  
14585933 M.H.Woo, C.Losasso, H.Guo, L.Pattarello, P.Benedetti, and M.A.Bjornsti (2003).
Locking the DNA topoisomerase I protein clamp inhibits DNA rotation and induces cell lethality.
  Proc Natl Acad Sci U S A, 100, 13767-13772.  
14654701 M.O.Christensen, H.U.Barthelmes, F.Boege, and C.Mielke (2003).
Residues 190-210 of human topoisomerase I are required for enzyme activity in vivo but not in vitro.
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12853620 P.B.Arimondo, S.Angenault, L.Halby, A.Boutorine, F.Schmidt, C.Monneret, T.Garestier, J.S.Sun, C.Bailly, and C.Hélène (2003).
Spatial organization of topoisomerase I-mediated DNA cleavage induced by camptothecin-oligonucleotide conjugates.
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Position-specific trapping of topoisomerase II by benzo[a]pyrene diol epoxide adducts: implications for interactions with intercalating anticancer agents.
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