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== '''Introduction''' == | == '''Introduction''' == | ||
[[Image:AG85C homodimer.jpg |100 xp|left|thumb|'''Figure 1.''' Ag85C homodimer. ]] | [[Image:AG85C homodimer.jpg |100 xp|left|thumb|'''Figure 1.''' Ag85C homodimer. ]] | ||
[http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ''Mycobacterium tuberculosis''] is the bacteria that causes the [http://www.mayoclinic.org/diseases-conditions/tuberculosis/basics/definition/con-20021761 tuberculosis] (TB) disease itself, a leading infectious cause of death world-wide. Thus, it is necessary to develop antimycobacterial drugs. However, this has proven to be difficult as the bacteria can become resistant as a result of misuse of drugs. This gives the bacteria time to mutate which ultimately leads to the drug resistance. To combat this, scientists and researchers have taken on many studies and clinical trials to locate specific drug targets. Obstacles for controlling TB infection include lengthy treatment regimens, drug resistance, lack of a highly efficacious vaccine, and incomplete understanding of the factors that control virulence and disease progression.<ref> Online Mendelian Inheritance in Man (OMIM). Mycobacterium tuberculosis, susceptibility to. [Internet]. Baltimore (MD): Johns Hopkins University; 2014 Nov 12 [cited 2015 March 16]. Available from http://www.omim.org/entry/607948 </ref> Of these projects, some deal specifically with the ''M. tuberculosis'' [http://onlinelibrary.wiley.com/doi/10.1046/j.1472-765x.2002.01091.x/epdf Antigen 85] (Ag85) complex. Ag85 complex consists of 3 secreted enzymes (A, B, and C) and plays a key role in pathogenesis and cell wall synthesis of ''M. tuberculosis''. <ref name="Favrot"/> | [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ''Mycobacterium tuberculosis''] is the bacteria that causes the [http://www.mayoclinic.org/diseases-conditions/tuberculosis/basics/definition/con-20021761 tuberculosis] (TB) disease itself, a leading infectious cause of death world-wide. Thus, it is necessary to develop antimycobacterial drugs. However, this has proven to be difficult as the bacteria can become resistant as a result of misuse of drugs. This gives the bacteria time to mutate which ultimately leads to the drug resistance. To combat this, scientists and researchers have taken on many studies and clinical trials to locate specific drug targets. Obstacles for controlling TB infection include lengthy treatment regimens, drug resistance, lack of a highly efficacious vaccine, and incomplete understanding of the factors that control virulence and disease progression.<ref> Online Mendelian Inheritance in Man (OMIM). Mycobacterium tuberculosis, susceptibility to. [Internet]. Baltimore (MD): Johns Hopkins University; 2014 Nov 12 [cited 2015 March 16]. Available from http://www.omim.org/entry/607948 </ref> Of these projects, some deal specifically with the ''M. tuberculosis'' [http://onlinelibrary.wiley.com/doi/10.1046/j.1472-765x.2002.01091.x/epdf Antigen 85] (Ag85) complex. Ag85 complex consists of 3 secreted enzymes (A, B, and C) and plays a key role in pathogenesis and cell wall synthesis of ''M. tuberculosis''. <ref name="Favrot"> PMID:25028518 </ref> | ||
The [http://www.hindawi.com/journals/jir/2011/405310.fig.001.jpg cell wall of mycobacterium tuberculosis] covalently linked molecules, one of which is [https://en.wikipedia.org/wiki/Mycolic_acid mycolic acid], a fatty acid which exists in the membrane as the free glycolipids trehalose monomycolate (TMM) and [http://en.wikipedia.org/wiki/Trehalose_dimycolate trehalose dimycolate] (TDM). Studies suggest that these three components are necessary to maintain the integrity of the cell wall.<ref name="Gobec">PMID:15177473</ref> More specifically, Ag85C is important in the generation of the bacterial cell wall in that it transfers the necessary mycolic acid to the rest of the Ag85 complex, and thus it is suggested that the enzyme displays mycolyltransferace activity. Specifically, the Ag85 enzymes catalyze the transfer of a mycolyl residue from one molecule of α, α-trehalose monomycolate (TMM) to another TMM, leading to the [http://biology.kenyon.edu/BMB/Jmol2009/KatandSuzanne/TDM-Formation.jpg formation of TDM]. Trehalose is necessary for proper growth of the bacterial cells. Thus, there is potential to target these enzymes with specific drugs to prevent the spread of the disease.<ref name="Favrot"/> | The [http://www.hindawi.com/journals/jir/2011/405310.fig.001.jpg cell wall of mycobacterium tuberculosis] covalently linked molecules, one of which is [https://en.wikipedia.org/wiki/Mycolic_acid mycolic acid], a fatty acid which exists in the membrane as the free glycolipids trehalose monomycolate (TMM) and [http://en.wikipedia.org/wiki/Trehalose_dimycolate trehalose dimycolate] (TDM). Studies suggest that these three components are necessary to maintain the integrity of the cell wall.<ref name="Gobec">PMID:15177473</ref> More specifically, Ag85C is important in the generation of the bacterial cell wall in that it transfers the necessary mycolic acid to the rest of the Ag85 complex, and thus it is suggested that the enzyme displays mycolyltransferace activity. Specifically, the Ag85 enzymes catalyze the transfer of a mycolyl residue from one molecule of α, α-trehalose monomycolate (TMM) to another TMM, leading to the [http://biology.kenyon.edu/BMB/Jmol2009/KatandSuzanne/TDM-Formation.jpg formation of TDM]. Trehalose is necessary for proper growth of the bacterial cells. Thus, there is potential to target these enzymes with specific drugs to prevent the spread of the disease.<ref name="Favrot"/> | ||