9GEF

Experimental localization of metal-binding sites reveals the role of metal ions in the delafloxacin-stabilized Streptococcus pneumoniae topoisomerase IV DNA cleavage complex

Summary for 9GEF

• Entry DOI: 10.2210/pdb9gef/pdb
• Descriptor: DNA TOPOISOMERASE (ATP-HYDROLYZING),DNA TOPOISOMERASE 4, ACETATE ION, delafloxacin, ... (12 entities in total)
• Functional Keywords: metal ions; type ii topoisomerases; fluoroquinolones; long-wavelength x-ray crystallography, dna binding protein
• Biological source: Streptococcus pneumoniae; More
• Total number of polymer chains: 6
• Total formula weight: 176703.96

Authors

Wang, B.,Najmudin, S.,Pan, X.-S.,Mykhaylyk, V.,Orr, C.,Wagner, A.,Govada, L.,Chayen, N.E.,Fisher, L.M.,Sanderson, M.R. (deposition date: 2024-08-08, release date: 2024-10-16)

Primary citation

Wang, B.,Najmudin, S.,Pan, X.S.,Mykhaylyk, V.,Orr, C.,Wagner, A.,Govada, L.,Chayen, N.E.,Fisher, L.M.,Sanderson, M.R.
Experimental localization of metal-binding sites reveals the role of metal ions in type II DNA topoisomerases.
Proc.Natl.Acad.Sci.USA, 121:e2413357121-e2413357121, 2024

PubMed Abstract: Metal ions have important roles in supporting the catalytic activity of DNA-regulating enzymes such as topoisomerases (topos). Bacterial type II topos, gyrases and topo IV, are primary drug targets for fluoroquinolones, a class of clinically relevant antibacterials requiring metal ions for efficient drug binding. While the presence of metal ions in topos has been elucidated in biochemical studies, accurate location and assignment of metal ions in structural studies have historically posed significant challenges. Recent advances in X-ray crystallography address these limitations by extending the experimental capabilities into the long-wavelength range, exploiting the anomalous contrast from light elements of biological relevance. This breakthrough enables us to confirm experimentally the locations of Mg in the fluoroquinolone-stabilized topo IV complex. Moreover, we can unambiguously identify the presence of K and Cl ions in the complex with one pair of K ions functioning as an additional intersubunit bridge. Overall, our data extend current knowledge on the functional and structural roles of metal ions in type II topos.

PubMed: 39361644
DOI: 10.1073/pnas.2413357121

Experimental method

X-RAY DIFFRACTION (2.62 Å)