6fqv

2.60A BINARY COMPLEX OF S.AUREUS GYRASE with UNCLEAVED DNA

spinqualitylabelsall models 6fqv, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6fqv is a 12 chain structure with sequence from Staan. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GOL, NA, SO4 Related: 5cdr Gene: gyrA, SA0006 (STAAN), gyrB, SA0005 (STAAN) Activity: DNA topoisomerase (ATP-hydrolyzing), with EC number 5.99.1.3 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [GYRA_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.[HAMAP-Rule:MF_01897] [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 Imidazopyrazinones (IPYs) are a new class of compounds that target bacterial topoisomerases as a basis for their antibacterial activity. We have characterized the mechanism of these compounds through structural/mechanistic studies showing they bind and stabilize a cleavage complex between DNA gyrase and DNA ('poisoning') in an analogous fashion to fluoroquinolones, but without the requirement for the water-metal-ion bridge. Biochemical experiments and structural studies of cleavage complexes of IPYs compared with an uncleaved gyrase-DNA complex, reveal conformational transitions coupled to DNA cleavage at the DNA gate. These involve movement at the GyrA interface and tilting of the TOPRIM domains toward the scissile phosphate coupled to capture of the catalytic metal ion. Our experiments show that these structural transitions are involved generally in poisoning of gyrase by therapeutic compounds and resemble those undergone by the enzyme during its adenosine triphosphate-coupled strand-passage cycle. In addition to resistance mutations affecting residues that directly interact with the compounds, we characterized a mutant (D82N) that inhibits formation of the cleavage complex by the unpoisoned enzyme. The D82N mutant appears to act by stabilizing the binary conformation of DNA gyrase with uncleaved DNA without direct interaction with the compounds. This provides general insight into the resistance mechanisms to antibiotics targeting bacterial type II topoisomerases. A new class of antibacterials, the imidazopyrazinones, reveal structural transitions involved in DNA gyrase poisoning and mechanisms of resistance.,Germe T, Voros J, Jeannot F, Taillier T, Stavenger RA, Bacque E, Maxwell A, Bax BD Nucleic Acids Res. 2018 Mar 10. pii: 4925761. doi: 10.1093/nar/gky181. PMID:29538767 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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