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Possible Acetylation of Tobramycin CoA Complex by Mycobacterium TuberculosisPossible Acetylation of Tobramycin CoA Complex by Mycobacterium Tuberculosis
- The study where this molecule was obtained was named "Aminoglycoside 2'-N-acetyltransferase from Mycobacterium tuberculosis-Complex with Coenzyme A and Tobramycin". The study showed that Tobramycin might have the possibility to change the oxidation state of mycobacteria and this might contribute to the effectiveness of tobramycin as an antibiotic. Researchers studied the possibility that the high affinity aminoglycoside complex may have the capability to acetylate a key biosynthetic intermediate of mycothiol. Mycothiol is a major reducing agent in the myobacteria. If this occurs it may participate in the regulation of cellular redox potential. A redox reaction or reduction-oxidation reactions are chemical reactions that changes the oxidation atom of the atom. An example of this would be the oxidation of a carbon atom to CO2. Oxidation is the loss of electrons or a gain oxidation state of the atom or molecule. A reduction is the gain of electrons or the decrease in oxidation state.
- Tobramycin is an antibiotic part of the aminoglycoside family. It was derived from Streptomyces tenebrarius. Tobramycin is targets a variety of bacteria particularly gram(-) species. Some of the more common side effects are ototoxicity and nephrotoxicity. Ototoxic meaning hearing loss and nephrotoxic meaning kidney damage. The kidney damage is due to Tobramycin reabsorption through the renal tubules. Tobramycin trade name is Tobrex. It is a pregnancy category D, making it not the best choice for patients who are pregnant. Tobramycin can be given intravenously, intramuscularly, as an inhalation or ophthalmicly. The chemical formula for Tobramycin is C18H37N5O9 and the molecular mass is 467.515 g/mol.
- This is a good representation of the . The active site is where the substrate, in this case tobramycin, binds to CoA and the mycobacterium to cause a reaction. The reaction researchers are anticipating in this study is the acetylation of the Mycothiol in the present in the mycobacteria.
- This molecule represents the . The alpha helices are represented with pink arrows and the beta strands are represented with yellow arrows. This molecule has approximately 13 alpha helices and approximetly 18 beta strands.
- The displayed in the molecule to the right are Coenzyme A, Tobramycin and 3'-Phosphate-Adenosine-5'-Diphosphate. (CoA) is a coenzyme that synthesizes and oxidizes fatty acids. IUPAC name is [(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-4-hydroxy-3-phosphonooxyoxolan-2-yl]methylphosphono hydrogen phosphate. The Protein in this molecule is represented as a . A dimer is a chemical structure formed from two subunits. In the molecule to the left you can see the representation of this.
- This structure focuses on the . The red molecules represent an anionic or negatively charged interaction. The dark blue molecules emphasize the cationic or positively charged interactions. The cationic and anionic interactions are contributed to arginine, aspartic acid, or glycine amino acids. The light blue molecules represent histidine, which is a basic amino acid.
- scene name='Sandbox_reserved_392/Hydrogen_bonds/2'>Hydrogen Bonds</scene> are attractive interactions (dipole-dipole) between an electronegative atom and hydrogen. The hydrogen bonds in this picture are displayed as yellow dashed lines. This bond always involves a hydrogen atom. A hydrogen bond is stronger then a van-der-waals interaction but weaker then an ionic or covalent bond. The hydrogen bonds in this display are between the alpha helices and beta sheets. An ionic bond is an attraction between two molecules of opposite charge. Covalent bonds, the strongest type of bond, involves the sharing of electrons between two molecules.
- Amino Acids:
Amino acids are the building blocks of proteins. There are 20 common amino acids. The contain and amine group (-NH2), a carboxylic acid group (-COOH) and a functional group specific to each amino acid. The functional group determines how the amino acid is classified. They are categorized as either, polar, non-polar, acidic or basic. There are 8 different amino acids present in the . CoA has a combination of 7 amino acids bound to it. The amino acids are two Arginine (basic amino acid), one Glycine (polar amino acid), and four Valine (non-polar amino acid). PAP has four amino acids bound to it, two Histidine and two tryptophan (non-polar amino acid). Tobramycin also has four amino acids bound to it, two aspartic acid (acidic amino acid)), Serine (polar amino acid) and tryptophan (non-polar amino acid)
CoA Amino Acids: In this representation it displays the covalent bond between . Arginine is displayed as the pink molecule and CoA is displayed as the orange and red molecule. Arginine classified as a basic amino acid and is a nonessential alpha amino acid, meaning that can be synthesized by the human body. are bound by a hydrogen bond, clearly displayed in this representation.
- References:
<Vetting, M. W., et al. "Aminoglycoside 2'-N-acetyltransferase from Mycobacterium tuberculosis-Complex with Coenzyme A and Tobramycin." RCSB Protien DataBase. N.p., 28 Aug.2002. Web. 13 July 2011. <http://www.rcsb.org/pdb/explore/explore.do?structureId=1M4D>.> Wikipedia. N.p., n.d. Web. 16 Sept. 2012. <http://en.wikipedia.org/wiki/Coenzyme_A>. Wikipedia. N.p., n.d. Web. 23 Sept. 2012. <http://en.wikipedia.org/wiki/Redox> Wikipedia. N.p., n.d. Web. 23 Sept. 2012. <http://en.wikipedia.org/wiki/Tobramycin>