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epimerox
Epimerox is an experimental broad-spectrum antibiotic compound being developed by scientists at the Rockefeller University and Astex Pharmaceuticals. It is a small molecule inhibitor compound that blocks the activity of the enzyme UDP-''N''-acetylglucosamine 2-epimerase, an epimerase enzyme〔(【引用サイトリンク】title=A New Era: The Fight Against Antibiotic-Resistant Pathogenic Bacteria )〕〔(【引用サイトリンク】title=New Anthrax-Killing Antibiotic Also Eliminates MRSA )〕 that is called ''2-epimerase'' for short.〔
==Mechanism of action==
2-Epimerase converts UDP-''N''-acetyl-D-glucosamine to UDP-''N''-acetyl-D-mannosamine. Bacterial 2-epimerase differs from its human counterpart in that the bacterial molecule has an allosteric site. For enzymatic activity, the allosteric site needs to be occupied by the substrate UDP-''N''-acetylglucosamine; this is the first enzyme described in which the substrate is present in both the catalytic and allosteric sites. Because epimerox targets the allosteric site of the bacterial 2-epimerase, low human toxicity is expected since the human 2-epimerase does not have this site.〔
Although epimerox was originally developed specifically to target ''Bacillus anthracis'', the bacterium that causes anthrax, it was found that it is also effective against methicillin-resistant ''Staphylococcus aureus'' (MRSA), and many other Gram-positive bacteria.〔〔(【引用サイトリンク】title=MRSA-killing Antibiotic Developed )〕
No bacteria could be identified that were resistant to the compound (resistance frequency of <10−11). Thus, epimerox is an antibiotic with low resistance potential. Therefore, 2-epimerase is a new antibiotic target to which resistance is a rare event. 2-Epimerase was discovered as a target because it was one of the enzymes in the biosynthetic pathway for synthesizing an essential neutral polysaccharide in the cell wall of ''B. anthracis'' (Glu:Gal-''N''Ac:Man-''N''Ac at a 3:2:1 ratio). This polysaccharide is only found in ''B. anthracis'' and is the receptor for a bacteriophage lysin enzyme called PlyG, which is produced by the γ-bacteriophage to release its progeny from infected ''B. anthracis''. For bacteriophage to survive they need to replicate inside a bacterial cell and release their progeny phage when they are assembled using their lysin. Since lysins from bacteriophage that infect Gram-positive bacteria must bind to a cell wall receptor to function, the enzymes have evolved over a billion years to identify substrate receptors in the bacterial cell wall that the bacteria cannot change easily. These substrates are either part of the peptidoglycan or sugars linked to it. Deletion of both 2-epimerase genes in ''B. anthracis'' is lethal to the bacterium.〔
抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』
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