4gee

Pyrrolopyrimidine inhibitors of DNA gyrase B and topoisomerase IV, part I: structure guided discovery and optimization of dual targeting agents with potent, broad-spectrum enzymatic activity.

spinqualitylabelsall models 4gee, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4gee is a 1 chain structure with sequence from Enterococcus faecalis v583. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 0WT, GOL Related: 4gfn, 4ggl, 4hxw, 4hxz, 4hy1, 4hym, 4hyp, 4hz0, 4hz5 Gene: gyrB, EF_0005 (Enterococcus faecalis V583) Activity: DNA topoisomerase (ATP-hydrolyzing), with EC number 5.99.1.3 Resources: FirstGlance, OCA, RCSB, PDBsum Function [Q839Z1_ENTFA] 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).[HAMAP-Rule:MF_01898] Publication Abstract from PubMed The bacterial topoisomerases DNA gyrase (GyrB) and topoisomerase IV (ParE) are essential enzymes that control the topological state of DNA during replication. The high degree of conservation in the ATP-binding pockets of these enzymes make them appealing targets for broad-spectrum inhibitor development. A pyrrolopyrimidine scaffold was identified from a pharmacophore-based fragment screen with optimization potential. Structural characterization of inhibitor complexes conducted using selected GyrB/ParE orthologs aided in the identification of important steric, dynamic and compositional differences in the ATP-binding pockets of the targets, enabling the design of highly potent pyrrolopyrimidine inhibitors with broad enzymatic spectrum and dual targeting activity. Pyrrolopyrimidine inhibitors of DNA gyrase B (GyrB) and topoisomerase IV (ParE). Part I: Structure guided discovery and optimization of dual targeting agents with potent, broad-spectrum enzymatic activity.,Tari LW, Trzoss M, Bensen DC, Li X, Chen Z, Lam T, Zhang J, Creighton CJ, Cunningham ML, Kwan B, Stidham M, Shaw KJ, Lightstone FC, Wong SE, Nguyen TB, Nix J, Finn J Bioorg Med Chem Lett. 2012 Dec 5. pii: S0960-894X(12)01475-8. doi:, 10.1016/j.bmcl.2012.11.032. PMID:23352267 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Gyrase

Proteopedia Page Contributors and Editors (what is this?)

OCA