Sandbox Reserved 314
From Proteopedia
| Line 16: | Line 16: | ||
Geneticin, and other aminoglycosides, inhibit bacterial protein synthesis and are commonly used to treat infections induced by Gram-negative bacteria. <ref name="morris">PMID: 8663028</ref> | Geneticin, and other aminoglycosides, inhibit bacterial protein synthesis and are commonly used to treat infections induced by Gram-negative bacteria. <ref name="morris">PMID: 8663028</ref> | ||
Aminoglycosides are toxic to mammalian systems, primarily through kidney and ear-associated illnesses.<ref name="vicens">PMID: 12589761</ref> | Aminoglycosides are toxic to mammalian systems, primarily through kidney and ear-associated illnesses.<ref name="vicens">PMID: 12589761</ref> | ||
| - | Geneticin is more toxic to eukaroytic organisms than paromomycin, especially in the absence of an inactivating enzyme or targeted drug.2 | + | Geneticin is more toxic to eukaroytic organisms than paromomycin, especially in the absence of an inactivating enzyme or targeted drug.2 |
<Structure load='1mwl' size='250' frame='true' align='right' caption='Trial2' scene='Insert optional scene name here' /> | <Structure load='1mwl' size='250' frame='true' align='right' caption='Trial2' scene='Insert optional scene name here' /> | ||
Revision as of 15:46, 29 March 2011
| This Sandbox is Reserved from January 10, 2010, through April 10, 2011 for use in BCMB 307-Proteins course taught by Andrea Gorrell at the University of Northern British Columbia, Prince George, BC, Canada. |
To get started:
More help: Help:Editing |
Geneticin
Contents |
Geneticin, also known as gentamicin or G418, belongs to a group of positively charged sugar derivatives known as aminoglycosides. Aminoglycosides contain three rings that possess hydroxyl, ammonium, and methyl groups.[1] This group of proteins bind to different regions of the 30S particle of the ribosome interfering protein synthesis. The different regions of the ribosome they bind to depend on their chemical structures. Because geneticin is capable of binding to the 80S ribosome, it is known to be toxic to eukaryotic organisms. However, studies have shown that geneticin can be used in medicine to treat parasites and in the treatment of genetic disorders.
|
Structure
Geneticin contains three rings which are functionalized by hydroxyl, ammonium and methyl groups. When geneticin is bound to the eubacterial decoding A site, the complex is comprised of a double helix with 16 Watson-Crick pairs, two UU pairs, and two unpaired and four adenine bases. Rings I and II, together known as the neamine moiety, influences the adenine bases 1492 and 1943 of each site to turn away from the helix forming base triples with G-C pairs. In site I and II, 14 hydrogen bonds occur between geneticin and the base atoms and phosphate oxygen atoms of the A site. Flipped out adenine bases 1492 and 1493 allow Ring I to intercalate inside the helix and is stabilized by stacking against G1491. The phosphate groups of the bulged adenine bases are hydrogen bonded to two hydroxyl groups. Intramolecular hydrogen bonds occur between Ring II and the other two rings and ammonium N3 is completely dehydrated.
Function
Geneticin, and other aminoglycosides, inhibit bacterial protein synthesis and are commonly used to treat infections induced by Gram-negative bacteria. [2] Aminoglycosides are toxic to mammalian systems, primarily through kidney and ear-associated illnesses.[1] Geneticin is more toxic to eukaroytic organisms than paromomycin, especially in the absence of an inactivating enzyme or targeted drug.2
|
References
- ↑ 1.0 1.1 Vicens Q, Westhof E. Crystal structure of geneticin bound to a bacterial 16S ribosomal RNA A site oligonucleotide. J Mol Biol. 2003 Feb 28;326(4):1175-88. PMID:12589761
- ↑ Morris JC, Ping-Sheng L, Zhai HX, Shen TY, Mensa-Wilmot K. Phosphatidylinositol phospholipase C is activated allosterically by the aminoglycoside G418. 2-deoxy-2-fluoro-scyllo-inositol-1-O-dodecylphosphonate and its analogs inhibit glycosylphosphatidylinositol phospholipase C. J Biol Chem. 1996 Jun 28;271(26):15468-77. PMID:8663028
2 Griffiths, J.K., Balakrishnan, R., Widmer, G., and Tzipori, S. 1998. Paromomycin and Geneticin inhibit intracellular Cryotosporidium parvum without trafficking through the host cell cytoplasm: implications for drug delivery. Infection and Immunity. 66:3874-3883.
