PDBsum entry: 1bjt

Topoisomerase

PDB id: 1bjt

Contents

Protein chain

679 a.a. *

Waters ×217

* Residue conservation analysis

PDB id:

1bjt

Name:

Topoisomerase

Title:

Topoisomerase ii residues 409-1201

Structure:

Topoisomerase ii. Chain: a. Fragment: DNA-binding and cleavage core, residues 409-1201. Engineered: yes

Source:

Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Expressed in: saccharomyces cerevisiae. Expression_system_taxid: 4932

Biol. unit:

Dimer (from PDB file)

Resolution:

2.50Å R-factor: 0.227 R-free: 0.269

Authors:

D.Fass,C.E.Bogden,J.M.Berger

Key ref:

D.Fass et al. (1999). Quaternary changes in topoisomerase II may direct orthogonal movement of two DNA strands. Nat Struct Biol, 6, 322-326. PubMed id: 10201398 DOI: 10.1038/7556

Date:

29-Jun-98 Release date: 04-May-99

Protein chain

P06786  (TOP2_YEAST) -  DNA topoisomerase 2

Seq: 1428 a.a.

Struc: 679 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.5.99.1.3 - Dna topoisomerase (ATP-hydrolyzing).
• Reaction: ATP-dependent breakage, passage and rejoining of double-stranded DNA.

 Gene Ontology (GO) functional annotation 

• Cellular component: chromosome (1 term)
• Biological process: DNA metabolic process (3 terms)
• Biochemical function: DNA binding (4 terms)

DOI no: 10.1038/7556

Nat Struct Biol 6:322-326 (1999)

PubMed id: 10201398

Quaternary changes in topoisomerase II may direct orthogonal movement of two DNA strands.

D.Fass, C.E.Bogden, J.M.Berger.

ABSTRACT

Type II DNA topoisomerases mediate the passage of one DNA duplex through a transient break in another, an event essential for chromosome segregation and cell viability. The active sites of the type II topoisomerase dimer associate covalently with the DNA break-points and must separate by at least the width of the second DNA duplex to accommodate transport. A new structure of the Saccharomyces cerevisiae topoisomerase II DNA-binding and cleavage core suggests that in addition to conformational changes in the DNA-opening platform, a dramatic reorganization of accessory domains may occur during catalysis. These conformational differences have implications for both the DNA-breaking and duplex-transport events in the topo II reaction mechanism, suggest a mechanism by which two distinct drug-resistance loci interact, and illustrate the scope of structural changes in the cycling of molecular machines.

Selected figure(s)

Figure 3.
Figure 3. Stereo diagrams of the B' domains, and side views in the context of the topo II DNA-binding and cleavage core. a, T2O B' orientation. Each B' hook (orange) packs near the opposite active-site tyrosine (ball-and-stick). The Rossmann fold (red) makes limited contacts to the A' shoulder of its own protomer. b, T2M orientation. The associations seen in T2O are reversed such that the B' hook packs against the A' head of its own protomer, while the Rossmann fold contacts the opposite shoulder. In the side view, the B' domains have partially exposed the DNA-binding groove at the top of the A' subfragments. Within the B' domains themselves, a modest hinge motion changes the relative positions of the hook and Rossmann fold between T2O and T2M. c, Model for the orientation of the B' domains in a T2C-type topo II structure^14. In this model, conserved acidic residues in the B' domains lie close to the active-site tyrosines. In the side view, the DNA-binding groove is completely exposed.

Figure 4.
Figure 4. Schematic illustration of a proposed B' domain rotation within the global catalytic mechanism. The topo II 'C' state is based on the GyrA A' structure^12 and the relationship between domain I and the active-site tyrosine observed in E. coli DNA topoisomerase I^14, ^18. This state is proposed to bind the uncleaved G segment and promote DNA cleavage. The 'M' conformations are based on T2M and represents a DNA-cleaved and partially opened state of the A' subfragments. Rotation of the B' domains may aid transport of the T segment as they approach the T2O conformation. The 'O' state represents a fully open A' arrangement with the T segment stored in the central hole^11. The B' subfragments are red and orange, and the A' subfragments are blue. The ATPase domains are indicated in yellow, and are absent from the 'M' panel for clarity.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (1999, 6, 322-326) copyright 1999.

Figures were selected by an automated process.