7Z9C

E.coli gyrase holocomplex with 217 bp DNA and albicidin

7Z9C の概要

• エントリーDOI: 10.2210/pdb7z9c/pdb
• EMDBエントリー: 14570
• 分子名称: DNA gyrase subunit A, DNA gyrase subunit B, DNA (5'-D(P*AP*AP*AP*TP*CP*TP*GP*TP*GP*CP*GP*GP*GP*T)-3'), ... (9 entities in total)
• 機能のキーワード: type ii topoisomerase, antibiotic, albicidin, dna gyrase, isomerase
• 由来する生物種: Escherichia coli str. K-12 substr. MG1655; 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 397973.30

構造登録者

Ghilarov, D.,Heddle, J.G.H.,Suessmuth, R. (登録日: 2022-03-21, 公開日: 2023-02-15, 最終更新日: 2024-11-13)

主引用文献

Michalczyk, E.,Hommernick, K.,Behroz, I.,Kulike, M.,Pakosz-Stepien, Z.,Mazurek, L.,Seidel, M.,Kunert, M.,Santos, K.,von Moeller, H.,Loll, B.,Weston, J.B.,Mainz, A.,Heddle, J.G.,Sussmuth, R.D.,Ghilarov, D.
Molecular mechanism of topoisomerase poisoning by the peptide antibiotic albicidin.
Nat Catal, 6:52-67, 2023

PubMed Abstract: The peptide antibiotic albicidin is a DNA topoisomerase inhibitor with low-nanomolar bactericidal activity towards fluoroquinolone-resistant Gram-negative pathogens. However, its mode of action is poorly understood. We determined a 2.6 Å resolution cryoelectron microscopy structure of a ternary complex between topoisomerase DNA gyrase, a 217 bp double-stranded DNA fragment and albicidin. Albicidin employs a dual binding mechanism where one end of the molecule obstructs the crucial gyrase dimer interface, while the other intercalates between the fragments of cleaved DNA substrate. Thus, albicidin efficiently locks DNA gyrase, preventing it from religating DNA and completing its catalytic cycle. Two additional structures of this trapped state were determined using synthetic albicidin analogues that demonstrate improved solubility, and activity against a range of gyrase variants and topoisomerase IV. The extraordinary promiscuity of the DNA-intercalating region of albicidins and their excellent performance against fluoroquinolone-resistant bacteria holds great promise for the development of last-resort antibiotics.

PubMed: 36741192
DOI: 10.1038/s41929-022-00904-1

実験手法

ELECTRON MICROSCOPY (3.06 Å)