PDBsum entry: 3foe

Isomerase/DNA

PDB id: 3foe

Contents

Protein chains

432 a.a. *

196 a.a. *

DNA/RNA

Ligands

NFX ×2

* Residue conservation analysis

PDB id:

3foe

Name:

Isomerase/DNA

Title:

Structural insight into the quinolone-DNA cleavage complex of type iia topoisomerases

Structure:

DNA topoisomerase 4 subunit a. Chain: a, b. Fragment: residues 1-488. Synonym: parc55, topoisomerase iv subunit a. Engineered: yes. DNA topoisomerase 4 subunit b. Chain: c, d. Fragment: residues 404-647. Synonym: pare30, topoisomerase iv subunit b.

Source:

Streptococcus pneumoniae. Organism_taxid: 1313. Gene: parc, sp_0855. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: pare, sp_0852. Synthetic: yes. Synthetic: yes

Resolution:

4.00Å R-factor: 0.264 R-free: 0.313

Authors:

I.Laponogov,M.K.Sohi,D.A.Veselkov,X.-S.Pan,R.Sawhney, A.W.Thompson,K.E.Mcauley,L.M.Fisher,M.R.Sanderson

Key ref:

I.Laponogov et al. (2009). Structural insight into the quinolone-DNA cleavage complex of type IIA topoisomerases. Nat Struct Biol, 16, 667-669. PubMed id: 19448616 DOI: 10.1038/nsmb.1604

Date:

30-Dec-08 Release date: 24-Feb-09

Protein chains

P72525  (PARC_STRPN) -  DNA topoisomerase 4 subunit A

Seq: 823 a.a.

Struc: 432 a.a.*

Protein chains

Q59961  (PARE_STRPN) -  DNA topoisomerase 4 subunit B

Seq: 647 a.a.

Struc: 196 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 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/nsmb.1604

Nat Struct Biol 16:667-669 (2009)

PubMed id: 19448616

Structural insight into the quinolone-DNA cleavage complex of type IIA topoisomerases.

I.Laponogov, M.K.Sohi, D.A.Veselkov, X.S.Pan, R.Sawhney, A.W.Thompson, K.E.McAuley, L.M.Fisher, M.R.Sanderson.

ABSTRACT

Type II topoisomerases alter DNA topology by forming a covalent DNA-cleavage complex that allows DNA transport through a double-stranded DNA break. We present the structures of cleavage complexes formed by the Streptococcus pneumoniae ParC breakage-reunion and ParE TOPRIM domains of topoisomerase IV stabilized by moxifloxacin and clinafloxacin, two antipneumococcal fluoroquinolones. These structures reveal two drug molecules intercalated at the highly bent DNA gate and help explain antibacterial quinolone action and resistance.

Selected figure(s)

Figure 1.
(a) Domain organization of S. pneumoniae topo IV. (b,c) Front (b) and top (c) views of the topo IV ParC55 and ParE30 proteins complexed with the G-segment DNA and a quinolone drug (moxifloxacin), shown both in surface (above) and detailed cartoon (below) representations. DNA is in green, the TOPRIM domain (ParE30) is in yellow and the ParC55 is in blue. The drug molecules are shown in red. The WHD, 'tower' and C-gate are shown in cyan, orange and silver, respectively. The interface region between ParC and ParE subunits (involving the 1 helix) is in purple. (d,e) Chemical representation of moxifloxacin (d) and clinafloxacin (e), respectively. Generated using VMD^20 and POV-Ray (http://www.povray.org).

Figure 2.
(a) Front, top and side views of the cleavage complex active site in cartoon representation. The 4 helices are shown in blue. Moxifloxacin is in red. The DNA G-segment is in green with the backbone positions relative to the cleavage point, indicated by yellow numbers in green circles. The active site tyrosines (Tyr118) are in orange and the residues thought to be involved in coordination of the active site magnesium ion are shown in purple. The residues responsible for drug resistance upon mutation are shown in yellow—Ser79 and Asp83 are located within the 4 helix of ParC WHD, whereas Glu474, Glu475, Arg456 and Asp435 (A, D, B and C, respectively) reside within the TOPRIM domain of ParE. The rest of the protein molecule is shown in silver. Rendered using VMD and Pov-Ray. (b) Top, bottom and side views of the cleaved G-segment DNA molecule (green) tethered to the active site tyrosines (orange) with the moxifloxacin (red) molecules intercalated. The superimposed [A]-weighted 2F[o] – F[c] (blue) and F[o] – F[c] (yellow) electron density maps are contoured at 1.5 and 3.2 , respectively. Rendered using WinCoot^21 and POV-Ray (http://www.povray.org/).

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2009, 16, 667-669) copyright 2009.