5J5P

AMP-PNP-stabilized ATPase domain of topoisomerase IV from Streptococcus pneumoniae, complex type I

Summary for 5J5P

• Entry DOI: 10.2210/pdb5j5p/pdb
• Descriptor: DNA topoisomerase 4 subunit B, DNA (5'-D(*GP*CP*GP*CP*GP*C)-3'), PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... (6 entities in total)
• Functional Keywords: streptococcus pneumoniae, topoisomerase iv, dna binding, isomerase, isomerase-dna complex, atpase domain, t-segment, isomerase/dna
• Biological source: Streptococcus pneumoniae; More
• Total number of polymer chains: 6
• Total formula weight: 98461.33

Authors

Laponogov, I.,Pan, X.-S.,Skamrova, G.,Umrekar, T.,Fisher, L.M.,Sanderson, M.R. (deposition date: 2016-04-03, release date: 2017-07-26, Last modification date: 2024-01-10)

Primary citation

Laponogov, I.,Pan, X.S.,Veselkov, D.A.,Skamrova, G.B.,Umrekar, T.R.,Fisher, L.M.,Sanderson, M.R.
Trapping of the transport-segment DNA by the ATPase domains of a type II topoisomerase.
Nat Commun, 9:2579-2579, 2018

PubMed Abstract: Type II topoisomerases alter DNA topology to control DNA supercoiling and chromosome segregation and are targets of clinically important anti-infective and anticancer therapeutics. They act as ATP-operated clamps to trap a DNA helix and transport it through a transient break in a second DNA. Here, we present the first X-ray crystal structure solved at 2.83 Å of a closed clamp complete with trapped T-segment DNA obtained by co-crystallizing the ATPase domain of S. pneumoniae topoisomerase IV with a nonhydrolyzable ATP analogue and 14-mer duplex DNA. The ATPase dimer forms a 22 Å protein hole occupied by the kinked DNA bound asymmetrically through positively charged residues lining the hole, and whose mutagenesis impacts the DNA decatenation, DNA relaxation and DNA-dependent ATPase activities of topo IV. These results and a side-bound DNA-ParE structure help explain how the T-segment DNA is captured and transported by a type II topoisomerase, and reveal a new enzyme-DNA interface for drug discovery.

PubMed: 29968711
DOI: 10.1038/s41467-018-05005-x

Experimental method

X-RAY DIFFRACTION (1.97 Å)