6yd9 | pdb_00006yd9

Ecoli GyrB24 with inhibitor 16a

spinqualitylabelsall models 6yd9, resolution 1.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6yd9 is a 1 chain structure with sequence from "bacillus_coli"_migula_1895 "bacillus coli" migula 1895. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: EDO, ON2 Gene: gyrB, acrB, cou, himB, hisU, nalC, parA, pcbA, b3699, JW5625 ("Bacillus coli" Migula 1895) Activity: DNA topoisomerase, with EC number 5.6.2.2 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [GYRB_ECOLI] 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. Publication Abstract from PubMed We designed and synthesized a series of inhibitors of the bacterial enzymes DNA gyrase and DNA topoisomerase IV, based on our recently published benzothiazole-based inhibitor bearing an oxalyl moiety. To improve the antibacterial activity and retain potent enzymatic activity, we systematically explored the chemical space. Several strategies of modification were followed: varying substituents on the pyrrole carboxamide moiety, alteration of the central scaffold, including variation of substitution position and, most importantly, modification of the oxalyl moiety. Compounds with acidic, basic, and neutral properties were synthesized. To understand the mechanism of action and binding mode, we have obtained a crystal structure of compound 16a, bearing a primary amino group, in complex with the N-terminal domain of E. coli gyrase B (24 kDa) (PDB: 6YD9). Compound 15a, with a low molecular weight of 383 Da, potent inhibitory activity on E. coli gyrase (IC50 = 9.5 nM), potent antibacterial activity on E. faecalis (MIC = 3.13 muM), and efflux impaired E. coli strain (MIC = 0.78 muM), is an important contribution for the development of novel gyrase and topoisomerase IV inhibitors in Gram-negative bacteria. Exploring the Chemical Space of Benzothiazole-Based DNA Gyrase B Inhibitors.,Skok Z, Barancokova M, Benek O, Cruz CD, Tammela P, Tomasic T, Zidar N, Masic LP, Zega A, Stevenson CEM, Mundy JEA, Lawson DM, Maxwell A, Kikelj D, Ilas J ACS Med Chem Lett. 2020 Oct 15;11(12):2433-2440. doi:, 10.1021/acsmedchemlett.0c00416. eCollection 2020 Dec 10. PMID:33329764 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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