SORA

Advancing, promoting and sharing knowledge of health through excellence in teaching, clinical practice and research into the prevention and treatment of illness

Structure of an 'open' clamp type II topoisomerase-DNA complex provides a mechanism for DNA capture and transport

Laponogov, I; Veselkov, DA; Crevel, IM; Pan, XS; Fisher, LM; Sanderson, MR (2013) Structure of an 'open' clamp type II topoisomerase-DNA complex provides a mechanism for DNA capture and transport. NUCLEIC ACIDS RESEARCH, 41 (21). 9911 - 9923 (13). ISSN 0305-1048 https://doi.org/10.1093/nar/gkt749
SGUL Authors: Fisher, Larry Mark Laponogov, Ivan Pan, Xiao Su

[img]
Preview
PDF Published Version
Download (1MB) | Preview

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 β-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 Å, the highest resolution achieved for the full complex to date, and illuminates the mechanism of DNA capture and transport by a type II topoisomerase.

Item Type: Article
Additional Information: Copyright © The Author(s) 2013. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Adenosine Triphosphatases, Adenosine Triphosphate, Binding Sites, Biological Transport, DNA, DNA Topoisomerase IV, Models, Molecular, Protein Structure, Tertiary, Streptococcus pneumoniae, Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, BIOCHEMISTRY & MOLECULAR BIOLOGY, STREPTOCOCCUS-PNEUMONIAE, CRYSTAL-STRUCTURES, GYRASE, IV, INHIBITION, CRYSTALLOGRAPHY, RESISTANCE, SYSTEM, FLUOROQUINOLONES, DETERMINANTS
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Cell Sciences (INCCCS)
Journal or Publication Title: NUCLEIC ACIDS RESEARCH
ISSN: 0305-1048
Related URLs:
Dates:
DateEvent
1 November 2013Published
PubMed ID: 23965305
Web of Science ID: 23965305
Download EPMC Full text (PDF)
Download EPMC Full text (HTML)
Go to PubMed abstract
URI: http://openaccess.sgul.ac.uk/id/eprint/103417
Publisher's version: https://doi.org/10.1093/nar/gkt749

Actions (login required)

Edit Item Edit Item