6fm4 | pdb_00006fm4

The crystal structure of S. aureus Gyrase complex with ID-130 and DNA

spinqualitylabelsall models 6fm4, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6fm4 is a 4 chain structure with sequence from Staan. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 5UA, DU5, MN Gene: gyrA, SA0006 (STAAN) Activity: DNA topoisomerase (ATP-hydrolyzing), with EC number 5.99.1.3 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [GYRB_STAAN] DNA gyrase negatively supercoils closed circular double-stranded DNA in an ATP-dependent manner and also catalyzes the interconversion of other topological isomers of double-stranded DNA rings, including catenanes and knotted rings (By similarity). Publication Abstract from PubMed Bacterial resistance is increasing rapidly, requiring urgent identification of new antibacterial drugs that are effective against multidrug-resistant pathogens. Novel bacterial topoisomerase inhibitors (NBTIs) provide a new strategy for investigating the well validated DNA gyrase and topoisomerase IV targets, while preventing cross resistance issues. On this basis, starting from a virtual screening campaign and subsequent structure-based hit optimization guided by X-ray studies, a novel class of piperazine-like NBTIs with outstanding enzymatic activity against Staphylococcus aureus and Escherichia coli DNA gyrase and topoisomerase IV was identified. Notably, compounds (+/-)-33, (+/-)-35, and (+/-)-36 with potent and balance multitarget enzymatic profiles, exhibited excellent efficacy against selected Gram-positive and Gram-negative pathogens, as well as clinically relevant resistant strains. Overall, the new NBTI chemotype described herein, thanks to the broad-spectrum antibacterial activity and the favourable in vitro safety profile, might serve as a basis for the development of novel treatments against serious infections. Virtual Screening Approach and Investigation of Structure Activity Relationships to Discover Novel Bacterial Topoisomerase Inhibitors (NBTIs) Targeting Gram-Positive and Gram-Negative Pathogens.,Magaro' G, Prati F, Garofalo B, Corso G, Furlotti G, Apicella C, Mangano G, D'Atanasio N, Robinson D, Di Giorgio FP, Ombrato R J Med Chem. 2019 Jul 5. doi: 10.1021/acs.jmedchem.9b00394. PMID:31276392 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Gyrase 3D Structures

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