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Isomerase PDB id
1zxm
Jmol
Contents
Protein chains
373 a.a. *
Ligands
ANP ×2
Metals
_MG ×2
Waters ×528
* Residue conservation analysis
PDB id:
1zxm
Name: Isomerase
Title: Human topo iia atpase/amp-pnp
Structure: DNA topoisomerase ii, alpha isozyme. Chain: a, b. Synonym: topo iia atpase. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: top2a, top2. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
Resolution:
1.87Å     R-factor:   0.220     R-free:   0.243
Authors: H.Wei,A.J.Ruthenburg,S.K.Bechis,G.L.Verdine
Key ref:
H.Wei et al. (2005). Nucleotide-dependent domain movement in the ATPase domain of a human type IIA DNA topoisomerase. J Biol Chem, 280, 37041-37047. PubMed id: 16100112 DOI: 10.1074/jbc.M506520200
Date:
08-Jun-05     Release date:   23-Aug-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P11388  (TOP2A_HUMAN) -  DNA topoisomerase 2-alpha
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1531 a.a.
373 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.5.99.1.3  - Dna topoisomerase (ATP-hydrolyzing).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP-dependent breakage, passage and rejoining of double-stranded DNA.
 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: 10.1074/jbc.M506520200 J Biol Chem 280:37041-37047 (2005)
PubMed id: 16100112  
 
 
Nucleotide-dependent domain movement in the ATPase domain of a human type IIA DNA topoisomerase.
H.Wei, A.J.Ruthenburg, S.K.Bechis, G.L.Verdine.
 
  ABSTRACT  
 
Type IIA DNA topoisomerases play multiple essential roles in the management of higher-order DNA structure, including modulation of topological state, chromosome segregation, and chromatin condensation. These diverse physiologic functions are all accomplished through a common molecular mechanism, wherein the protein catalyzes transient cleavage of a DNA duplex (the G-segment) to yield a double-stranded gap through which another duplex (the T-segment) is passed. The overall process is orchestrated by the opening and closing of molecular "gates" in the topoisomerase structure, which is regulated by ATP binding, hydrolysis, and release of ADP and inorganic phosphate. Here we present two crystal structures of the ATPase domain of human DNA topoisomerase IIalpha in different nucleotide-bound states. Comparison of these structures revealed rigid-body movement of the structural modules within the ATPase domain, suggestive of the motions of a molecular gate.
 
  Selected figure(s)  
 
Figure 1.
FIGURE 1. Overall structure of the 46-kDa ATPase domain of human topoisomerase II (HT2ATPase) (residues 29-428) bound to AMPPNP (A-C) and ADP (D-F). A and D, ribbon drawings emphasizing the modularity of the protein structure. Each of the four modules in the HT2ATPase homodimer is colored individually: blue and cyan, ATPase modules; magenta and peach, transducer modules. One protomer of HT2ATPase is blue and magenta; the other is cyan and peach. Asterisks denote the -hairpin motif, unique to eukaryotic Topo II enzymes, which forms the upper end of the DNA channel. B and E, surface representation in the same orientation as A and D, with the -hairpin shown in yellow. Red in underlying ribbon trace indicates C-terminal portions of the structure that become ordered in the ADP-bound state. C and F, surface drawing rotated by 90° about the x axis with respect to B and E, looking inward from the C terminus-proximal end of the cavity. 		Figure 2.
FIGURE 2. Analysis of nucleotide-dependent domain movement in HT2ATPase. A, least-squares superposition of the two protomers in the asymmetric unit of the AMPPNP structure. B, superposition of the four protomers in the asymmetric unit of the ADP structure. C, superposition of the dimers of the AMPPNP (blue) and ADP (yellow) structures. The magnitude of domain rotation and translation is indicated. Red X indicates the approximate pivot point for rigid-body rotation. D and E, superposition of the individual (D) nucleotide-binding and (E) transducer modules in the AMPPNP structure and ADP structure (coloring as in C).
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2005, 280, 37041-37047) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21419530 K.Y.Jun, E.Y.Lee, M.J.Jung, O.H.Lee, E.S.Lee, H.Y.Park Choo, Y.Na, and Y.Kwon (2011).
Synthesis, biological evaluation, and molecular docking study of 3-(3'-heteroatom substituted-2'-hydroxy-1'-propyloxy) xanthone analogues as novel topoisomerase IIα catalytic inhibitor.
  Eur J Med Chem, 46, 1964-1971.  
20675723 A.J.Schoeffler, A.P.May, and J.M.Berger (2010).
A domain insertion in Escherichia coli GyrB adopts a novel fold that plays a critical role in gyrase function.
  Nucleic Acids Res, 38, 7830-7844.
PDB code: 3nuh
19603203 C.E.Cassidy, and W.N.Setzer (2010).
Cancer-relevant biochemical targets of cytotoxic Lonchocarpus flavonoids: a molecular docking analysis.
  J Mol Model, 16, 311-326.  
20200034 C.García-Estrada, C.F.Prada, C.Fernández-Rubio, F.Rojo-Vázquez, and R.Balaña-Fouce (2010).
DNA topoisomerases in apicomplexan parasites: promising targets for drug discovery.
  Proc Biol Sci, 277, 1777-1787.  
  20703329 J.E.Deweese, and N.Osheroff (2010).
The use of divalent metal ions by type II topoisomerases.
  Metallomics, 2, 450-459.  
20127325 P.Xie (2010).
Dynamics of strand passage catalyzed by topoisomerase II.
  Eur Biophys J, 39, 1251-1259.  
20855424 Y.Li, Y.Luan, X.Qi, M.Li, L.Gong, X.Xue, X.Wu, Y.Wu, M.Chen, G.Xing, J.Yao, and J.Ren (2010).
Emodin triggers DNA double-strand breaks by stabilizing topoisomerase II-DNA cleavage complexes and by inhibiting ATP hydrolysis of topoisomerase II.
  Toxicol Sci, 118, 435-443.  
19377505 J.L.Nitiss (2009).
DNA topoisomerase II and its growing repertoire of biological functions.
  Nat Rev Cancer, 9, 327-337.  
19128485 P.Chène, J.Rudloff, J.Schoepfer, P.Furet, P.Meier, Z.Qian, J.M.Schlaeppi, R.Schmitz, and T.Radimerski (2009).
Catalytic inhibition of topoisomerase II by a novel rationally designed ATP-competitive purine analogue.
  BMC Chem Biol, 9, 1.  
19155278 T.R.Collins, G.G.Hammes, and T.S.Hsieh (2009).
Analysis of the eukaryotic topoisomerase II DNA gate: a single-molecule FRET and structural perspective.
  Nucleic Acids Res, 37, 712-720.  
18755053 A.J.Schoeffler, and J.M.Berger (2008).
DNA topoisomerases: harnessing and constraining energy to govern chromosome topology.
  Q Rev Biophys, 41, 41.  
18403371 F.Mueller-Planitz, and D.Herschlag (2008).
Coupling between ATP binding and DNA cleavage by DNA topoisomerase II: A unifying kinetic and structural mechanism.
  J Biol Chem, 283, 17463-17476.  
18647240 N.D.Thomsen, and J.M.Berger (2008).
Structural frameworks for considering microbial protein- and nucleic acid-dependent motor ATPases.
  Mol Microbiol, 69, 1071-1090.  
17681352 A.K.McClendon, and N.Osheroff (2007).
DNA topoisomerase II, genotoxicity, and cancer.
  Mutat Res, 623, 83-97.  
17603498 K.D.Corbett, P.Benedetti, and J.M.Berger (2007).
Holoenzyme assembly and ATP-mediated conformational dynamics of topoisomerase VI.
  Nat Struct Mol Biol, 14, 611-619.
PDB code: 2q2e
16549872 K.L.Gilroy, C.Leontiou, K.Padget, J.H.Lakey, and C.A.Austin (2006).
mAMSA resistant human topoisomerase IIbeta mutation G465D has reduced ATP hydrolysis activity.
  Nucleic Acids Res, 34, 1597-1607.  
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.