4emv | pdb_00004emv

Crystal structure of a topoisomerase ATP inhibitor

spinqualitylabelsall models 4emv, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4emv is a 1 chain structure with sequence from Streptococcus pneumoniae ga47373. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 0R9 Related: 4em7 Gene: ParE, SPAR94_0831 (Streptococcus pneumoniae GA47373) Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed We present the discovery and optimization of a novel series of bacterial topoisomerase inhibitors. Starting from a virtual screening hit, activity was optimized through a combination of structure-based design and physical property optimization. Synthesis of fewer than a dozen compounds was required to achieve inhibition of the growth of methicillin-resistant Staphyloccus aureus (MRSA) at compound concentrations of 1.56muM. These compounds simultaneously inhibit DNA gyrase and Topoisomerase IV at similar nanomolar concentrations, reducing the likelihood of the spontaneous occurrence of target-based mutations resulting in antibiotic resistance, an increasing threat in the treatment of serious infections. Discovery of a novel azaindole class of antibacterial agents targeting the ATPase domains of DNA gyrase and Topoisomerase IV.,Manchester JI, Dussault DD, Rose JA, Boriack-Sjodin PA, Uria-Nickelsen M, Ioannidis G, Bist S, Fleming P, Hull KG Bioorg Med Chem Lett. 2012 Aug 1;22(15):5150-6. Epub 2012 Jun 19. PMID:22814212 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Topoisomerase

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