Sandbox reserved 392: Difference between revisions
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== Possible Acetylation of Tobramycin CoA Complex by Mycobacterium Tuberculosis == | |||
== | <StructureSection load='1m4d' size='500' side='right' caption='Structure of HMG-CoA reductase (PDB entry [[1dq8]])' scene=''>The study where this molecule was obtained is named "Aminoglycoside 2'-N-acetyltransferase from Mycobacterium tuberculosis-Complex with Coenzyme A and Tobramycin". The study suggested a reason for Tobramycin resistance. The resistance may be due to the possible acetylation of mycobacteria by Tobramycin. When Tobramycin acetylates it loses its function. The reason for the acetylation is not fully understood but a possible explanation may be that the mycobacteria needs to be acetylated so that a key biosynthetic intermediate, Mycothiol can be activated. Mycothiol is a major reducing agent in the myobacteria. <ref>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</ref> | ||
If this occurs it may participate in the regulation of cellular redox potential. A redox reaction or reduction-oxidation reaction is a chemical reaction that changes the oxidation state 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 in the oxidation state of the atom or molecule. A reduction is the gain of electrons or the decrease in oxidation state. <ref>Wikipedia. N.p., n.d. Web. 23 Sept. 2012. <Wikipedia. N.p., n.d. Web. 23 Sept. 2012. <http://en.wikipedia.org/wiki/Redox</ref> | |||
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===Secondary Structures=== | ===Secondary Structures=== | ||
This molecule represents the <scene name='Sandbox_reserved_392/Color_protein_secondarystruct/1'>alpha helices and beta strands</scene>. The alpha helices are represented with pink arrows and the beta strands are represented with yellow arrows. This molecule has approximately four alpha helices and two beta strands. The structure of the alpha and beta sheets in this structure represents the GNAT fold. The GNAT fold is almost completely catalyzed by CoA- dependent transfer of an acyl group to an exposed amino acid group. This interaction is the basis for the study. This shows how the acetylation of Mycothiol is occurring and why. | This molecule represents the <scene name='Sandbox_reserved_392/Color_protein_secondarystruct/1'>alpha helices and beta strands</scene>. The alpha helices are represented with pink arrows and the beta strands are represented with yellow arrows. This molecule has approximately four alpha helices and two beta strands. The structure of the alpha and beta sheets in this structure represents the GNAT fold. The GNAT fold is almost completely catalyzed by CoA- dependent transfer of an acyl group to an exposed amino acid group. This interaction is the basis for the study. This shows how the acetylation of Mycothiol is occurring and why.<ref>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</ref> | ||
===Ligands=== | ===Ligands=== | ||
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===Active Site=== | ===Active Site=== | ||
The active site of a molecule can be described as a pocket where interaction between structures causes a desired effect. This is a good representation of the <scene name='Sandbox_reserved_392/ | The active site of a molecule can be described as a pocket where interaction between structures causes a desired effect. This is a good representation of the <scene name='Sandbox_reserved_392/Active_site/2'>active site</scene>. The active site is where the substrate, in this case tobramycin, binds to CoA and the mycobacterium to cause an antibacterial effect. It the study described this is where the acetylation of the mycothiol should be occurring. | ||
== Amino Acids== | == 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 <scene name='Sandbox_reserved_392/Original_untouched_molecule/1'>Tobramycin-CoA molecule</scene>. 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) | 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.<ref>Wikipedia. N.p., n.d. Web. 17 October. 2012. <Wikipedia. N.p., n.d. Web. 23 Sept. 2012. <http://en.wikipedia.org/wiki/Amino_acid</ref> There are 8 different amino acids present in the <scene name='Sandbox_reserved_392/Original_untouched_molecule/1'>Tobramycin-CoA molecule</scene>. 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).<ref>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</ref> | ||
===CoA Amino Acids=== | ===CoA Amino Acids=== | ||
In this representation it displays the | In this representation it displays the interaction between <scene name='Sandbox_reserved_392/Arg124_bond_to_coa/3'>CoA and Arginine</scene>. Arginine is displayed as the pink molecule and CoA is displayed as the orange and red molecule. Arginine is classified as a basic, nonessential amino acid. Nonessential meaning the human body can synthesize it. | ||
<scene name='Sandbox_reserved_392/Val92_and_coa/ | |||
<scene name='Sandbox_reserved_392/Val92_and_coa/2'>Val96 and CoA</scene> are clearly displayed in this representation. Valine is a nonpolar amino acid. Unlike Arginine, Valine is an essential amino acid. <ref>Vetting, M. W., et al. "Aminoglycoside 2'-N-acetyltransferase from Mycobacterium tuberculosis-Complex with Coenzyme A and Tobramycin." RCSB Protein DataBase. N.p., 28 Aug.2002. Web. 13 July 2011.<http://www.rcsb.org/pdb/explore/explore.do?structureId=1M4D</ref> | |||
===PAP Amino Acids=== | ===PAP Amino Acids=== | ||
This shows <scene name='Sandbox_reserved_392/Pap_and_his54/ | This shows <scene name='Sandbox_reserved_392/Pap_and_his54/2'>His 54 and PAP</scene> interaction.Histidine is the smallest amino acid. I is also classified as an essential amino acid. | ||
The other Amino acid bound to PAP | The other Amino acid bound to PAP is <scene name='Sandbox_reserved_392/Trp90_and_pap/2'>Typ90</scene>. Tryptophan is an essential amino acid. Tryptophan is a precursor to serotonin which is a key neurotransmitter in the gastrointestinal tract, platelets, and the central nervous system (CNS). <ref>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</ref> | ||
= References = | = References = | ||
{{Reflist}} | {{Reflist}} | ||
</StructureSection> | |||