3wru

Crystal structure of the bacterial ribosomal decoding site in complex with synthetic aminoglycoside with F-HABA group

spinqualitylabelsall models 3wru, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3wru is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: K, SJP Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed Aminoglycoside antibiotics are pseudosaccharides decorated with ammonium groups that are critical for their potent broad-spectrum antibacterial activity. Despite over three decades of speculation whether or not modulation of pKa is a viable strategy to curtail aminoglycoside kidney toxicity, there is a lack of methods to systematically probe amine-RNA interactions and resultant cytotoxicity trends. This study reports the first series of potent aminoglycoside antibiotics harboring fluorinated N1-hydroxyaminobutyryl acyl (HABA) appendages for which fluorine-RNA contacts are revealed through an X-ray cocrystal structure within the RNA A-site. Cytotoxicity in kidney-derived cells was significantly reduced for the derivative featuring our novel beta,beta-difluoro-HABA group, which masks one net charge by lowering the pKa without compromising antibacterial potency. This novel side-chain assists in evasion of aminoglycoside-modifying enzymes, and it can be easily transferred to impart these properties onto any number of novel analogs. Toxicity modulation, resistance enzyme evasion, and A-site X-ray structure of broad-spectrum antibacterial neomycin analogs.,Maianti JP, Kanazawa H, Dozzo P, Matias RD, Feeney LA, Armstrong ES, Hildebrandt DJ, Kane TR, Gliedt MJ, Goldblum AA, Linsell MS, Aggen JB, Kondo J, Hanessian S ACS Chem Biol. 2014 Sep 19;9(9):2067-73. doi: 10.1021/cb5003416. Epub 2014 Jul, 14. PMID:25019242 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA