Summary information and primary citation
- PDB-id
- 7lhz; SNAP-derived features in text and JSON formats;
DNAproDB
- Class
- isomerase-DNA-inhibitor
- Method
- X-ray (3.3 Å)
- Summary
- K. pneumoniae topoisomerase iv (pare-parc) in complex with DNA and (3s)-10-[(3r)-3-(1-aminocyclopropyl)pyrrolidin-1-yl]-9-fluoro-3-methyl-5-oxo-2,3-dihydro-5h-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid (compound 25)
- Reference
- Lapointe G, Skepper CK, Holder LM, Armstrong D, Bellamacina C, Blais J, Bussiere D, Bian J, Cepura C, Chan H, Dean CR, De Pascale G, Dhumale B, Fisher LM, Fulsunder M, Kantariya B, Kim J, King S, Kossy L, Kulkarni U, Lakshman J, Leeds JA, Ling X, Lvov A, Ma S, Malekar S, McKenney D, Mergo W, Metzger L, Mhaske K, Moser HE, Mostafavi M, Namballa S, Noeske J, Osborne C, Patel A, Patel D, Patel T, Piechon P, Polyakov V, Prajapati K, Prosen KR, Reck F, Richie DL, Sanderson MR, Satasia S, Savani B, Selvarajah J, Sethuraman V, Shu W, Tashiro K, Thompson KV, Vaarla K, Vala L, Veselkov DA, Vo J, Vora B, Wagner T, Wedel L, Williams SL, 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." J.Med.Chem., 64, 6329-6357. doi: 10.1021/acs.jmedchem.1c00375.
- Abstract
- 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 compound
