The difficult case of crystallization and structure solution for the ParC55 breakage-reunion domain of topoisomerase IV from Streptococcus pneumoniae.

Autor: Maninder K Sohi, Dennis A Veselkov, Ivan Laponogov, Xiao-Su Pan, L Mark Fisher, Mark R Sanderson

Publikováno v: PLoS ONE, Vol 3, Iss 9, p e3201 (2008)

Streptococcus pneumoniae is the major cause of community-acquired pneumonia and is also associated with bronchitis, meningitis, otitis and sinusitis. The emergence and increasing prevalence of resistance to penicillin and other antibiotics has led to

Externí odkaz: https://doaj.org/article/a0a08757fa574262a43df4f00321df7d

Discovery and Optimization of DNA Gyrase and Topoisomerase IV Inhibitors with Potent Activity against Fluoroquinolone-Resistant Gram-Positive Bacteria

Autor: David McKenney, Louis E. Metzger, Dirksen E. Bussiere, Sylvia Ma, Ashish Patel, Bhavesh Dhumale, Upendra Kulkarni, Jay Parthiban Lakshman, Sean King, Duncan Armstrong, Kyuto Tashiro, Lauren Kossy, Tushar Patel, Lauren M. Holder, Jogitha Selvarajah, Sarah Williams, Satya Yendluri, Colin Osborne, Jason Vo, Mangesh Fulsunder, Xiaolan Ling, Laura Wedel, Gianfranco De Pascale, Jennifer A. Leeds, Cody Cepura, Heinz E. Moser, Alexey Rivkin, Sunil Namballa, Colin K. Skepper, Bhavin Kantariya, Mina Mostafavi, Bhautik Savani, Anatoli Lvov, Guillaume Lapointe, Cornelia Bellamacina, Bhavesh Vora, Daryl L. Richie, Helen Chan, Wosenu Mergo, Jianwei Bian, Wei Shu, Keshav Mhaske, Aregahegn Yifru, Mark R. Sanderson, Swapnil Malekar, Johanne Blais, Qin Yue, Yong Zhang, Katherine V. Thompson, Julie Kim, Charles R. Dean, Vijay Sethuraman, Trixie Wagner, L. Mark Fisher, Dennis A. Veselkov, Darshit Patel, Folkert Reck, Jonas Noeske, Krishniah Vaarla, Lakhan Vala, Shailesh Satasia, Krunal Prajapati, Philippe Piechon, Valery Polyakov, Katherine R Prosen

Publikováno v: Lapointe, G, Skepper, C K, Holder, L M, Armstrong, D, Bellamacina, C, Blais, J, Bussiere, D, Bian, J, Cepura, C, Chan, H, Dean, C R, De Pascale, G, Dhumale, B, Fisher, L M, Fulsunder, M, Kantariya, B, Kim, J, King, S, Kossy, L, Kulkarni, U, Lakshman, J, Leeds, J A, Ling, X, Lvov, A, Ma, S, Malekar, S, McKenney, D, Mergo, W, Metzger, L, Mhaske, K, Moser, H E, Mostafavi, M, Namballa, S, Noeske, J, Osborne, C, Patel, A, Patel, D, Patel, T, Piechon, P, Polyakov, V, Prajapati, K, Prosen, K R, Reck, F, Richie, D L, Sanderson, M R, Satasia, S, Savani, B, Selvarajah, J, Sethuraman, V, Shu, W, Tashiro, K, Thompson, K V, Vaarla, K, Vala, L, Veselkov, D A, Vo, J, Vora, B, Wagner, T, Wedel, L, Williams, S L, Yendluri, S, Yue, Q, Yifru, A, Zhang, Y & Rivkin, A 2021, ' Discovery and Optimization of DNA Gyrase and Topoisomerase IV Inhibitors with Potent Activity against Fluoroquinolone-Resistant Gram-Positive Bacteria ', Journal of Medicinal Chemistry, vol. 64, no. 9, pp. 6329-6357 . https://doi.org/10.1021/acs.jmedchem.1c00375

Herein, we describe the discovery and optimization of a novel series that inhibits bacterial DNA gyrase and topoisomerase IV via binding to, and stabilization of, DNA cleavage complexes. Optimization of this series led to the identification of compou

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::56db96726415696056387173baa99222
https://kclpure.kcl.ac.uk/en/publications/675d57ab-71d9-4244-886c-019cc57306cd

Trapping of the transport-segment DNA by the ATPase domains of a type II topoisomerase

Autor: Mark R. Sanderson, Trishant R. Umrekar, L. Mark Fisher, Galyna B. Skamrova, X.-S. Pan, D.A. Veselkov, Ivan Laponogov

Publikováno v: Nature Communications
Nature Communications, Vol 9, Iss 1, Pp 1-14 (2018)
Laponogov, I, Pan, X S, Veselkov, D A, Skamrova, G B, Umrekar, T R, Fisher, L M & Sanderson, M R 2018, ' Trapping of the transport-segment DNA by the ATPase domains of a type II topoisomerase ', Nature Communications, vol. 9, no. 1, 2579 . https://doi.org/10.1038/s41467-018-05005-x

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

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c07fda62f058b07219f98d4b18d977fc
http://europepmc.org/articles/PMC6030046

Structure of an ‘open’ clamp type II topoisomerase-DNA complex provides a mechanism for DNA capture and transport

Autor: Ivan Laponogov, L. Mark Fisher, Mark R. Sanderson, D.A. Veselkov, Xiao-Su Pan, Isabelle M.-T. Crevel

Publikováno v: Nucleic Acids Research

Type II topoisomerases regulate DNA supercoiling and chromosome segregation. They act as ATP-operated clamps that capture a DNA duplex and pass it through a transient DNA break in a second DNA segment via the sequential opening and closure of ATPase-

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::43147898f2868f6f21eaa319e7ff9e78
https://doi.org/10.1093/nar/gkt749

Probing the Differential Interactions of Quinazolinedione PD 0305970 and Quinolones with Gyrase and Topoisomerase IV

Autor: L. Mark Fisher, Katherine A. Gould, X.-S. Pan

Publikováno v: Antimicrobial Agents and Chemotherapy. 53:3822-3831

Quinazoline-2,4-diones, such as PD 0305970, are new DNA gyrase and topoisomerase IV (topo IV) inhibitors with potent activity against gram-positive pathogens, including quinolone-resistant isolates. The mechanistic basis of dione activity vis-à-vis

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::68291bc9bc8262b8d3663b6043441427
https://doi.org/10.1128/aac.00113-09