Sandbox Reserved 1068: Difference between revisions

Line 6:

==Introduction==

Salicylate synthase from ''Mycobacterim tuberculosis'' (MtbI) is a highly promiscuous enzyme that has four distinct activities ''in vivo'': isochorismate synthase (IS), isochorismate pyruvate lyase (IPL), salicylate synthase (SS) and chromate mutate (CM). MtbI belongs to the chorismate-utilising enzyme family, which consists of structural homologues (<scene name='69/694235/Irp9/2'>Ipr9</scene>, <scene name='69/694235/Menf/2'>MenF</scene>, <scene name='69/694235/Entc/2'>EntC</scene>, and <scene name='69/694235/Mbti/2'>MbtI</scene>) that isomerize chromate to isochorismate. These enzymes are present in bacteria, fungi, plants and apicomplexan parasites and catalyze the initial reactions of menaquinone, siderophore, and tryptophan biosynthesis. The IS, IPL, and SS activity of MbtI require the presence of a magnesium ion within the active site, while CM activity is only observed in absence of the magnesium cation. IS, IPL, and SS activity are also modulated by the pH of the medium. Isochorismate is the primary product at pH values below 7.5 and salicylate is the primary product formed at pH 8. The pH dependent activity of MbtI is related to the ionization state of the active site residues involved in the molecular mechanisms used by the enzyme to catalyze the different reactions<ref ~~name= "Gamma Chi"~~>PMID:23108268</ref>.

Salicylate synthase from ''Mycobacterim tuberculosis'' (MtbI) is a highly promiscuous enzyme that has four distinct activities ''in vivo'': isochorismate synthase (IS), isochorismate pyruvate lyase (IPL), salicylate synthase (SS) and chromate mutate (CM). MtbI belongs to the chorismate-utilising enzyme family, which consists of structural homologues (<scene name='69/694235/Irp9/2'>Ipr9</scene>, <scene name='69/694235/Menf/2'>MenF</scene>, <scene name='69/694235/Entc/2'>EntC</scene>, and <scene name='69/694235/Mbti/2'>MbtI</scene>) that isomerize chromate to isochorismate. These enzymes are present in bacteria, fungi, plants and apicomplexan parasites and catalyze the initial reactions of menaquinone, siderophore, and tryptophan biosynthesis. The IS, IPL, and SS activity of MbtI require the presence of a magnesium ion within the active site, while CM activity is only observed in absence of the magnesium cation. IS, IPL, and SS activity are also modulated by the pH of the medium. Isochorismate is the primary product at pH values below 7.5 and salicylate is the primary product formed at pH 8. The pH dependent activity of MbtI is related to the ionization state of the active site residues involved in the molecular mechanisms used by the enzyme to catalyze the different reactions<ref>PMID:23108268</ref>.

The salicylate synthase activity of MbtI catalyzes the first committed step in the synthesis of the iron chelating siderophore, mycobactin, in ''Mycobacterium tuberculosis''(Figure 3)<ref>PMID:22607697</ref>. This complex secondary metabolite is essential for both virulence and survival of ''M. tuberculosis''. Therefore, inhibitors of salicylate synthase may serve as potential TB therapies with a novel mode of action.

The salicylate synthase activity of MbtI catalyzes the first committed step in the synthesis of the iron chelating siderophore, mycobactin, in ''Mycobacterium tuberculosis''(Figure 3)<ref name= "gamma chi">PMID:22607697</ref>. This complex secondary metabolite is essential for both virulence and survival of ''M. tuberculosis''. Therefore, inhibitors of salicylate synthase may serve as potential TB therapies with a novel mode of action.

Sandbox Reserved 1068: Difference between revisions

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools

@@ Line 6: / Line 6: @@
 ==Introduction==
-Salicylate synthase from ''Mycobacterim tuberculosis'' (MtbI) is a highly promiscuous enzyme that has four distinct activities ''in vivo'': isochorismate synthase (IS), isochorismate pyruvate lyase (IPL), salicylate synthase (SS) and chromate mutate (CM). MtbI belongs to the chorismate-utilising enzyme family, which consists of structural homologues (<scene name='69/694235/Irp9/2'>Ipr9</scene>, <scene name='69/694235/Menf/2'>MenF</scene>, <scene name='69/694235/Entc/2'>EntC</scene>, and <scene name='69/694235/Mbti/2'>MbtI</scene>) that isomerize chromate to isochorismate. These enzymes are present in bacteria, fungi, plants and apicomplexan parasites and catalyze the initial reactions of menaquinone, siderophore, and tryptophan biosynthesis.  The IS, IPL, and SS activity of MbtI require the presence of a magnesium ion within the active site, while CM activity is only observed in absence of the magnesium cation. IS, IPL, and SS activity are also modulated by the pH of the medium. Isochorismate is the primary product at pH values below 7.5 and salicylate is the primary product formed at pH 8. The pH dependent activity of MbtI is related to the ionization state of the active site residues involved in the molecular mechanisms used by the enzyme to catalyze the different reactions<ref name= "Gamma Chi">PMID:23108268</ref>.
+Salicylate synthase from ''Mycobacterim tuberculosis'' (MtbI) is a highly promiscuous enzyme that has four distinct activities ''in vivo'': isochorismate synthase (IS), isochorismate pyruvate lyase (IPL), salicylate synthase (SS) and chromate mutate (CM). MtbI belongs to the chorismate-utilising enzyme family, which consists of structural homologues (<scene name='69/694235/Irp9/2'>Ipr9</scene>, <scene name='69/694235/Menf/2'>MenF</scene>, <scene name='69/694235/Entc/2'>EntC</scene>, and <scene name='69/694235/Mbti/2'>MbtI</scene>) that isomerize chromate to isochorismate. These enzymes are present in bacteria, fungi, plants and apicomplexan parasites and catalyze the initial reactions of menaquinone, siderophore, and tryptophan biosynthesis.  The IS, IPL, and SS activity of MbtI require the presence of a magnesium ion within the active site, while CM activity is only observed in absence of the magnesium cation. IS, IPL, and SS activity are also modulated by the pH of the medium. Isochorismate is the primary product at pH values below 7.5 and salicylate is the primary product formed at pH 8. The pH dependent activity of MbtI is related to the ionization state of the active site residues involved in the molecular mechanisms used by the enzyme to catalyze the different reactions<ref>PMID:23108268</ref>.
-The salicylate synthase activity of MbtI catalyzes the first committed step in the synthesis of the iron chelating siderophore, mycobactin, in ''Mycobacterium tuberculosis''(Figure 3)<ref>PMID:22607697</ref>. This complex secondary metabolite is essential for both virulence and survival of ''M. tuberculosis''. Therefore, inhibitors of salicylate synthase may serve as potential TB therapies with a novel mode of action.
+The salicylate synthase activity of MbtI catalyzes the first committed step in the synthesis of the iron chelating siderophore, mycobactin, in ''Mycobacterium tuberculosis''(Figure 3)<ref name= "gamma chi">PMID:22607697</ref>. This complex secondary metabolite is essential for both virulence and survival of ''M. tuberculosis''. Therefore, inhibitors of salicylate synthase may serve as potential TB therapies with a novel mode of action.