Structural study of Topoisomerase IV-DNA-Levofloxacin complexes from Streptococcus pneumoniae

• Main Author: Wang Xilan
• Format: Article
• Language: English
• Published: EDP Sciences 2019-01-01
• Series: E3S Web of Conferences
• Online Access: https://www.e3s-conferences.org/articles/e3sconf/pdf/2019/57/e3sconf_chinabiofilms18_01021.pdf

S. pneumoniae is an important pathogen causing pulmonary infection, acute otitis media and purulent meningitis in infants and children. Type II topoisomerases are enzymes that play essential roles in DNA replication, chromosome segregation and recombination throughout all living organisms. Topoisomerases IV can make a transient break in DNA strands in one chromosome. These enzymes are very important antibacterial as well as anticancer targets and potential anti-trypanosomal targets. Levofloxacin has shown efficient inhibition of Type II topoisomerases in S. pneumoniae. Its mechanism of action is to inhibit the activity of DNA topoisomerase, prevent bacterial DNA synthesis and replication leading to bacterial death. We focused on solving the key structures of topoisomerase IV-DNA-levofloxacin complexes by negative staining electron microscopy and the resulting model was obtained at 32 Å by 3D autorefine in Relion 3.0. This study was to try and obtain the structure of the whole complex with DNA bound in the G-gate and the T-gate in order to study DNA capture and transport in type II topoisomerases.