3IFZ

crystal structure of the first part of the Mycobacterium tuberculosis DNA gyrase reaction core: the breakage and reunion domain at 2.7 A resolution

3IFZ の概要

• エントリーDOI: 10.2210/pdb3ifz/pdb
• 関連するPDBエントリー: 1AB4
• 分子名称: DNA gyrase subunit A, (4S)-2-METHYL-2,4-PENTANEDIOL, SODIUM ION, ... (4 entities in total)
• 機能のキーワード: dna gyrase, gyra, breakage and reunion domain, type ii topoisomerase, tuberculosis, quinolone binding site, dna binding site, antibiotic resistance, atp-binding, dna-binding, isomerase, nucleotide-binding, topoisomerase
• 由来する生物種: Mycobacterium tuberculosis
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 114233.07

構造登録者

Piton, J.,Aubry, A.,Delarue, M.,Mayer, C. (登録日: 2009-07-27, 公開日: 2010-07-28, 最終更新日: 2023-11-01)

主引用文献

Piton, J.,Petrella, S.,Delarue, M.,Andre-Leroux, G.,Jarlier, V.,Aubry, A.,Mayer, C.
Structural insights into the quinolone resistance mechanism of Mycobacterium tuberculosis DNA gyrase.
Plos One, 5:e12245-e12245, 2010

PubMed Abstract: Mycobacterium tuberculosis DNA gyrase, an indispensable nanomachine involved in the regulation of DNA topology, is the only type II topoisomerase present in this organism and is hence the sole target for quinolone action, a crucial drug active against multidrug-resistant tuberculosis. To understand at an atomic level the quinolone resistance mechanism, which emerges in extensively drug resistant tuberculosis, we performed combined functional, biophysical and structural studies of the two individual domains constituting the catalytic DNA gyrase reaction core, namely the Toprim and the breakage-reunion domains. This allowed us to produce a model of the catalytic reaction core in complex with DNA and a quinolone molecule, identifying original mechanistic properties of quinolone binding and clarifying the relationships between amino acid mutations and resistance phenotype of M. tuberculosis DNA gyrase. These results are compatible with our previous studies on quinolone resistance. Interestingly, the structure of the entire breakage-reunion domain revealed a new interaction, in which the Quinolone-Binding Pocket (QBP) is blocked by the N-terminal helix of a symmetry-related molecule. This interaction provides useful starting points for designing peptide based inhibitors that target DNA gyrase to prevent its binding to DNA.

PubMed: 20805881
DOI: 10.1371/journal.pone.0012245

実験手法

X-RAY DIFFRACTION (2.7 Å)