3wru: Difference between revisions
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''' | ==Crystal structure of the bacterial ribosomal decoding site in complex with synthetic aminoglycoside with F-HABA group== | ||
<StructureSection load='3wru' size='340' side='right' caption='[[3wru]], [[Resolution|resolution]] 2.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3wru]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WRU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3WRU FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=SJP:(2R,3R)-4-AMINO-N-[(1R,2S,3R,4R,5S)-5-AMINO-4-[(2,6-DIAMINO-2,3,4,6-TETRADEOXY-ALPHA-D-ERYTHRO-HEXOPYRANOSYL)OXY]-3-{[3-O-(2,6-DIAMINO-2,3,4,6-TETRADEOXY-BETA-L-THREO-HEXOPYRANOSYL)-BETA-D-RIBOFURANOSYL]OXY}-2-HYDROXYCYCLOHEXYL]-3-FLUORO-2-HYDROXYBUTANAMIDE'>SJP</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3wru FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wru OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3wru RCSB], [http://www.ebi.ac.uk/pdbsum/3wru PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:25019242</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Armstrong, E S.]] | |||
[[Category: Dozzo, P.]] | |||
[[Category: Feeney, L A.]] | |||
[[Category: Hanessian, S.]] | |||
[[Category: Kanazawa, H.]] | |||
[[Category: Kondo, J.]] | |||
[[Category: Maianti, J P.]] | |||
[[Category: Aminoglycoside]] | |||
[[Category: Ribosomal rna]] | |||
[[Category: Rna-antibiotic complex]] | |||
