Experimental localization of metal-binding sites reveals the role of metal ions in type II DNA topoisomerases.
Streptococcus pneumoniae
/ enzymology
Binding Sites
Crystallography, X-Ray
Magnesium
/ metabolism
Potassium
/ metabolism
Metals
/ metabolism
DNA Topoisomerases, Type II
/ metabolism
Fluoroquinolones
/ chemistry
Ions
/ metabolism
DNA Topoisomerase IV
/ metabolism
Models, Molecular
Bacterial Proteins
/ metabolism
Chlorides
/ metabolism
LW X-ray crystallography
fluoroquinolones
metal ions
topoisomerases
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
08 Oct 2024
08 Oct 2024
Historique:
medline:
4
10
2024
pubmed:
4
10
2024
entrez:
3
10
2024
Statut:
ppublish
Résumé
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
Identifiants
pubmed: 39361644
doi: 10.1073/pnas.2413357121
doi:
Substances chimiques
Magnesium
I38ZP9992A
Potassium
RWP5GA015D
Metals
0
DNA Topoisomerases, Type II
EC 5.99.1.3
Fluoroquinolones
0
Ions
0
DNA Topoisomerase IV
EC 5.99.1.-
Bacterial Proteins
0
Chlorides
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2413357121Subventions
Organisme : Medical Research Centre (MRC)
ID : MR/T000848
Déclaration de conflit d'intérêts
Competing interests statement:The authors declare no competing interest.