Sandbox Reserved 1053: Difference between revisions
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Mutagenesis studies have confirmed the Ag85C functions through a Glu-His-Ser <scene name='69/694220/Catalytic_triad/4'>catalytic triad</scene>, similar to that of [http://en.wikipedia.org/wiki/Chymotrypsin chymotrypsin]. By modifying each of the catalytic residues separately testing the enzyme’s relative activity, it has been shown that mutation of any one of these residues dramatically reduces activity. The S124 alcohol’s nucleophilicity is inductively strengthened through H260 and E224, which allows the S124 residue to catalyze a reaction that involves [http://en.wikipedia.org/wiki/Cord_factor trehalose 6, 6’-dimycolate]. The formation of the functional catalytic triad relies on upon Van der Waals interaction between C209 and the peptide bond between L232 and T231. This interaction results in a kinked conformation of the α9 helix, which promotes that activity of the catalytic triad. As a result, Ag85C, a mycolyl transferase, can facilitate the modification of trehalose monomycolates to trehalose dimycolates, which are then transported to the bacterial cell wall. This reaction is shown in the figure below. | Mutagenesis studies have confirmed the Ag85C functions through a Glu-His-Ser <scene name='69/694220/Catalytic_triad/4'>catalytic triad</scene>, similar to that of [http://en.wikipedia.org/wiki/Chymotrypsin chymotrypsin]. By modifying each of the catalytic residues separately testing the enzyme’s relative activity, it has been shown that mutation of any one of these residues dramatically reduces activity. The S124 alcohol’s nucleophilicity is inductively strengthened through H260 and E224, which allows the S124 residue to catalyze a reaction that involves [http://en.wikipedia.org/wiki/Cord_factor trehalose 6, 6’-dimycolate]. The formation of the functional catalytic triad relies on upon Van der Waals interaction between C209 and the peptide bond between L232 and T231. This interaction results in a kinked conformation of the α9 helix, which promotes that activity of the catalytic triad. As a result, Ag85C, a mycolyl transferase, can facilitate the modification of trehalose monomycolates to trehalose dimycolates, which are then transported to the bacterial cell wall. This reaction is shown in the figure below. | ||
[[Image:Mech_Ag85C.jpeg|400 px|center|'''Figure 3:''' General reaction catalyzed by Antigen 85C]] | [[Image:Mech_Ag85C.jpeg|400 px|center|thumb|'''Figure 3:''' General reaction catalyzed by Antigen 85C]] | ||
== Methods of Inhibition == | == Methods of Inhibition == | ||
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Additional thiol-modifying agents, [http://en.wikipedia.org/wiki/4-Chloromercuribenzoic_acid p-chloromercuribenzoic acid] and [http://en.wikipedia.org/wiki/Iodoacetamide iodoacetamide], were crystalized with Ag85C. The structures show that each of these thiol-reactive inhibitors covalently bound to C209 and caused a relaxation of the α9 helix in a similar fashion to ebselen. | Additional thiol-modifying agents, [http://en.wikipedia.org/wiki/4-Chloromercuribenzoic_acid p-chloromercuribenzoic acid] and [http://en.wikipedia.org/wiki/Iodoacetamide iodoacetamide], were crystalized with Ag85C. The structures show that each of these thiol-reactive inhibitors covalently bound to C209 and caused a relaxation of the α9 helix in a similar fashion to ebselen. | ||
[[Image:Inhibitors_Ag85c.jpeg|400 px|center]] | [[Image:Inhibitors_Ag85c.jpeg|400 px|center|thumb|'''Figure 6:''' Known thiol-reactive inhibitors of Ag85C]] | ||
</StructureSection> | </StructureSection> | ||