9FZ6

A 2.58A crystal structure of S. aureus DNA gyrase and DNA with metals identified through anomalous scattering

Summary for 9FZ6

• Entry DOI: 10.2210/pdb9fz6/pdb
• Descriptor: DNA gyrase subunit A, DNA gyrase subunit B, DNA (5'-D(*AP*GP*CP*CP*GP*TP*AP*G)-3'), ... (8 entities in total)
• Functional Keywords: type iia topoisomerase, isomerase, dna, metals
• Biological source: Staphylococcus aureus; More
• Total number of polymer chains: 8
• Total formula weight: 166760.88

Authors

Morgan, H.,Duman, R.,Bax, B.D.,Warren, A.J. (deposition date: 2024-07-04, release date: 2024-10-23, Last modification date: 2024-11-27)

Primary citation

Morgan, H.,Nicholls, R.A.,Warren, A.J.,Ward, S.E.,Evans, G.,Long, F.,Murshudov, G.N.,Duman, R.,Bax, B.D.
How Do Gepotidacin and Zoliflodacin Stabilize DNA Cleavage Complexes with Bacterial Type IIA Topoisomerases? 1. Experimental Definition of Metal Binding Sites.
Int J Mol Sci, 25:-, 2024

PubMed Abstract: One of the challenges for experimental structural biology in the 21st century is to see chemical reactions happen. () DNA gyrase is a type IIA topoisomerase that can create temporary double-stranded DNA breaks to regulate DNA topology. Drugs, such as gepotidacin, zoliflodacin and the quinolone moxifloxacin, can stabilize these normally transient DNA strand breaks and kill bacteria. Crystal structures of uncleaved DNA with a gepotidacin precursor (2.1 Å GSK2999423) or with doubly cleaved DNA and zoliflodacin (or with its progenitor QPT-1) have been solved in the same P6 space-group (a = b ≈ 93 Å, c ≈ 412 Å). This suggests that it may be possible to observe the two DNA cleavage steps (and two DNA-religation steps) in this P6 space-group. Here, a 2.58 Å anomalous manganese dataset in this crystal form is solved, and four previous crystal structures (1.98 Å, 2.1 Å, 2.5 Å and 2.65 Å) in this crystal form are re-refined to clarify crystal contacts. The structures clearly suggest a single moving metal mechanism-presented in an accompanying (second) paper. A previously published 2.98 Å structure of a yeast topoisomerase II, which has static disorder around a crystallographic twofold axis, was published as containing two metals at one active site. Re-refined coordinates of this 2.98 Å yeast structure are consistent with other type IIA topoisomerase structures in only having one metal ion at each of the two different active sites.

PubMed: 39519241
DOI: 10.3390/ijms252111688

Experimental method

X-RAY DIFFRACTION (2.58 Å)