7mvs

DNA gyrase complexed with uncleaved DNA and Compound 7 to 2.6A resolutionDNA gyrase complexed with uncleaved DNA and Compound 7 to 2.6A resolution

Structural highlights 7mvs is a 4 chain structure with sequence from Staphylococcus aureus and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.6013715Å Ligands: , , , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GYRB_STAAU 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.[HAMAP-Rule:MF_01898]GYRA_STAAU A type II topoisomerase that negatively supercoils closed circular double-stranded (ds) DNA in an ATP-dependent manner to modulate DNA topology and maintain chromosomes in an underwound state. Negative supercoiling favors strand separation, and DNA replication, transcription, recombination and repair, all of which involve strand separation. Also able to catalyze the interconversion of other topological isomers of dsDNA rings, including catenanes and knotted rings. Type II topoisomerases break and join 2 DNA strands simultaneously in an ATP-dependent manner.[HAMAP-Rule:MF_01897] Publication Abstract from PubMed Novel bacterial topoisomerase inhibitors (NBTIs) are among the most promising new antibiotics in preclinical/clinical development. We previously reported dioxane-linked NBTIs with potent antistaphylococcal activity and reduced hERG inhibition, a key safety liability. Herein, polarity-focused optimization enabled the delineation of clear structure-property relationships for both microsomal metabolic stability and hERG inhibition, resulting in the identification of lead compound 79. This molecule demonstrates potent antibacterial activity against diverse Gram-positive pathogens, inhibition of both DNA gyrase and topoisomerase IV, a low frequency of resistance, a favorable in vitro cardiovascular safety profile, and in vivo efficacy in a murine model of methicillin-resistant Staphylococcus aureus infection. Optimization of TopoIV Potency, ADMET Properties, and hERG Inhibition of 5-Amino-1,3-dioxane-Linked Novel Bacterial Topoisomerase Inhibitors: Identification of a Lead with In Vivo Efficacy against MRSA.,Lu Y, Vibhute S, Li L, Okumu A, Ratigan SC, Nolan S, Papa JL, Mann CA, English A, Chen A, Seffernick JT, Koci B, Duncan LR, Roth B, Cummings JE, Slayden RA, Lindert S, McElroy CA, Wozniak DJ, Yalowich J, Mitton-Fry MJ J Med Chem. 2021 Oct 28;64(20):15214-15249. doi: 10.1021/acs.jmedchem.1c01250. , Epub 2021 Oct 6. PMID:34614347 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Gyrase 3D Structures

spinqualitylabelsall models 7mvs, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image