Structural insight into negative DNA supercoiling by DNA gyrase, a bacterial type 2A DNA topoisomerase.
Nucleic Acids Res
; 41(16): 7815-27, 2013 Sep.
Article
em En
| MEDLINE
| ID: mdl-23804759
ABSTRACT
Type 2A DNA topoisomerases (Topo2A) remodel DNA topology during replication, transcription and chromosome segregation. These multisubunit enzymes catalyze the transport of a double-stranded DNA through a transient break formed in another duplex. The bacterial DNA gyrase, a target for broad-spectrum antibiotics, is the sole Topo2A enzyme able to introduce negative supercoils. We reveal here for the first time the architecture of the full-length Thermus thermophilus DNA gyrase alone and in a cleavage complex with a 155 bp DNA duplex in the presence of the antibiotic ciprofloxacin, using cryo-electron microscopy. The structural organization of the subunits of the full-length DNA gyrase points to a central role of the ATPase domain acting like a 'crossover trap' that may help to sequester the DNA positive crossover before strand passage. Our structural data unveil how DNA is asymmetrically wrapped around the gyrase-specific C-terminal ß-pinwheel domains and guided to introduce negative supercoils through cooperativity between the ATPase and ß-pinwheel domains. The overall conformation of the drug-induced DNA binding-cleavage complex also suggests that ciprofloxacin traps a DNA pre-transport conformation.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
DNA Super-Helicoidal
/
DNA Girase
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article