3wru
From Proteopedia
(Difference between revisions)
m (Protected "3wru" [edit=sysop:move=sysop]) |
|||
| Line 1: | Line 1: | ||
| - | ''' | + | ==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]] | ||
Revision as of 08:46, 5 November 2014
Crystal structure of the bacterial ribosomal decoding site in complex with synthetic aminoglycoside with F-HABA group
| |||||||||||
