Experimental localization of metal-binding sites reveals the role of metal ions in type II DNA 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
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

e2413357121

Subventions

Organisme : Medical Research Centre (MRC)
ID : MR/T000848

Déclaration de conflit d'intérêts

Competing interests statement:The authors declare no competing interest.

Auteurs

Beijia Wang (B)

Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London W12 0NN, United Kingdom.

Shabir Najmudin (S)

Molecular and Cellular Sciences Section, Neuroscience and Cell Biology Research Institute, St. George's, University of London, London SW17 0RE, United Kingdom.

Xiao-Su Pan (XS)

Molecular and Cellular Sciences Section, Neuroscience and Cell Biology Research Institute, St. George's, University of London, London SW17 0RE, United Kingdom.

Vitaliy Mykhaylyk (V)

Diamond Light Source, Harwell Science and Innovation Campus, Didcot OX11 0DE, United Kingdom.

Christian Orr (C)

Diamond Light Source, Harwell Science and Innovation Campus, Didcot OX11 0DE, United Kingdom.

Armin Wagner (A)

Diamond Light Source, Harwell Science and Innovation Campus, Didcot OX11 0DE, United Kingdom.

Lata Govada (L)

Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London W12 0NN, United Kingdom.

Naomi E Chayen (NE)

Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London W12 0NN, United Kingdom.

L Mark Fisher (LM)

Molecular and Cellular Sciences Section, Neuroscience and Cell Biology Research Institute, St. George's, University of London, London SW17 0RE, United Kingdom.

Mark R Sanderson (MR)

Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London W12 0NN, United Kingdom.
Molecular and Cellular Sciences Section, Neuroscience and Cell Biology Research Institute, St. George's, University of London, London SW17 0RE, United Kingdom.

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Classifications MeSH