PDBsum entry 4g0v

Go to PDB code: 
protein dna_rna ligands metals Protein-protein interface(s) links
Isomerase/DNA/isomerase inhibitor PDB id
Protein chain
663 a.a.
MIX ×2
_MG ×6
Waters ×559
PDB id:
Name: Isomerase/DNA/isomerase inhibitor
Title: Human topoisomerase iibeta in complex with DNA and mitoxantr
Structure: DNA topoisomerase 2-beta. Chain: a, b. Fragment: htop2beta cleavage core, unp residues 450-1206. Synonym: DNA topoisomerase ii, beta isozyme. Engineered: yes. DNA (5'-d(p Ap Gp Cp Cp Gp Ap Gp C)-3'). Chain: c, e. Engineered: yes. DNA (5'-d(p Tp Gp Cp Ap Gp Cp Tp Cp Gp Gp Cp T)-3
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: top2b. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Synthetic: yes
2.55Å     R-factor:   0.163     R-free:   0.206
Authors: C.C.Wu,T.K.Li,Y.C.Li,N.L.Chan
Key ref: C.C.Wu et al. (2013). On the structural basis and design guidelines for type II topoisomerase-targeting anticancer drugs. Nucleic Acids Res, 41, 10630-10640. PubMed id: 24038465 DOI: 10.1093/nar/gkt828
10-Jul-12     Release date:   17-Jul-13    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q02880  (TOP2B_HUMAN) -  DNA topoisomerase 2-beta
1626 a.a.
663 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - 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!
  Biological process     DNA metabolic process   2 terms 
  Biochemical function     DNA binding     4 terms  


DOI no: 10.1093/nar/gkt828 Nucleic Acids Res 41:10630-10640 (2013)
PubMed id: 24038465  
On the structural basis and design guidelines for type II topoisomerase-targeting anticancer drugs.
C.C.Wu, Y.C.Li, Y.R.Wang, T.K.Li, N.L.Chan.
Type II topoisomerases (Top2s) alter DNA topology via the formation of an enzyme-DNA adduct termed cleavage complex, which harbors a transient double-strand break in one DNA to allow the passage of another. Agents targeting human Top2s are clinically active anticancer drugs whose trapping of Top2-mediated DNA breakage effectively induces genome fragmentation and cell death. To understand the structural basis of this drug action, we previously determined the structure of human Top2 β-isoform forming a cleavage complex with the drug etoposide and DNA, and described the insertion of drug into DNA cleavage site and drug-induced decoupling of catalytic groups. By developing a post-crystallization drug replacement procedure that simplifies structural characterization of drug-stabilized cleavage complexes, we have extended the analysis toward other structurally distinct drugs, m-AMSA and mitoxantrone. Besides the expected drug intercalation, a switch in ribose puckering in the 3'-nucleotide of the cleavage site was robustly observed in the new structures, representing a new mechanism for trapping the Top2 cleavage complex. Analysis of drug-binding modes and the conformational landscapes of the drug-binding pockets provide rationalization of the drugs' structural-activity relationships and explain why Top2 mutants exhibit differential effects toward each drug. Drug design guidelines were proposed to facilitate the development of isoform-specific Top2-targeting anticancer agents.