4I3H: A Three-gate Structure Of Topoisomerase Iv From Streptococcus Pneumoniae

Citation:
Abstract
Type II topoisomerases regulate DNA supercoiling and chromosome segregation. They act as ATP-operated clamps that capture a DNA duplex and pass it through a transient DNA break in a second DNA segment via the sequential opening and closure of ATPase-, G-DNA- and C-gates. Here, we present the first 'open clamp' structures of a 3-gate topoisomerase II-DNA complex, the seminal complex engaged in DNA recognition and capture. A high-resolution structure was solved for a (full-length ParE-ParC55)2 dimer of Streptococcus pneumoniae topoisomerase IV bound to two DNA molecules: a closed DNA gate in a B-A-B form double-helical conformation and a second B-form duplex associated with closed C-gate helices at a novel site neighbouring the catalytically important beta-pinwheel DNA-binding domain. The protein N gate is present in an 'arms-wide-open' state with the undimerized N-terminal ParE ATPase domains connected to TOPRIM domains via a flexible joint and folded back allowing ready access both for gate and transported DNA segments and cleavage-stabilizing antibacterial drugs. The structure shows the molecular conformations of all three gates at 3.7 A, the highest resolution achieved for the full complex to date, and illuminates the mechanism of DNA capture and transport by a type II topoisomerase.
PDB ID: 4I3HDownload
MMDB ID: 112993
PDB Deposition Date: 2012/11/26
Updated in MMDB: 2013/12
Experimental Method:
x-ray diffraction
Resolution: 3.7  Å
Source Organism:
Streptococcus pneumoniae TIGR4
Similar Structures:
Biological Unit for 4I3H: hexameric; determined by author
Molecular Components in 4I3H
Label Count Molecule
Proteins (2 molecules)
2
Topoisomerase IV Subunit B, DNA Topoisomerase 4 Subunit a Chimera
Molecule annotation
Nucleotides(2 molecules)
2
DNA (5'- D(*cp*ap*ap*ap*gp*gp*cp*gp*gp*tp*ap*ap*tp*ap*cp*gp*gp*tp*tp*ap*tp*cp* Cp*ap*cp*ap*gp*ap*ap*tp*cp*ap*gp*g)-3')
Molecule annotation
2
DNA (5'- D(*cp*cp*tp*gp*ap*tp*tp*cp*tp*gp*tp*gp*gp*ap*tp*ap*ap*cp*cp*gp*tp*ap* Tp*tp*ap*cp*cp*gp*cp*cp*tp*tp*tp*g)-3')
Molecule annotation
Chemicals (3 molecules)
1
3
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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