Sandbox Reserved 1068: Difference between revisions

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==Inhibition Studies==

MbtI Inhibition studies aid in the future design of [http://psychology.wikia.com/wiki/Antitubercular_drugs anti-tubercular agents] and [http://en.wikipedia.org/wiki/Broad-spectrum_antibiotic broad-spectrum antibiotics] with a novel mode of action. Mimics of the enzyme-bound intermediate of MbtI, <scene name='69/694235/3sr6_inhibitor/3'>isochorismate</scene>, prove to be significantly more potent inhibitors than mimics of the substrate, chorismate <ref name= "1a"/>. The isochorismate mimic based on a 2,3-dihydroxybenzoate scaffold showed low-micromolar inhibition constants against MbtI that were an order of magnitude more potents than the natural substrates. The most potent inhibitors contained hydrophobic enol ether side chains at C3 instead of the enol-pyruvyl side chains seen in chorismate and isochorismate. <ref name="1a">PMID:20512795</ref> Increased potency of inhibitors with a substituted enolpyruvyl group has been attributed to a change in the binding mode through localized flexibility of the peptide backbone.

MbtI Inhibition studies aid in the future design of [http://psychology.wikia.com/wiki/Antitubercular_drugs anti-tubercular agents] and [http://en.wikipedia.org/wiki/Broad-spectrum_antibiotic broad-spectrum antibiotics] with a novel mode of action. Mimics of the enzyme-bound intermediate of MbtI, <scene name='69/694235/3sr6_inhibitor/3'>isochorismate</scene>, prove to be significantly more potent inhibitors than mimics of the substrate, chorismate <ref name= "1a"/><ref name="2a"/><ref name="5a"/>. The isochorismate mimic based on a 2,3-dihydroxybenzoate scaffold showed low-micromolar inhibition constants against MbtI that were an order of magnitude more potents than the natural substrates<ref name="2a"/>. The most potent inhibitors contained hydrophobic enol ether side chains at C3 instead of the enol-pyruvyl side chains seen in chorismate and isochorismate. <ref name="1a">PMID:20512795</ref> Increased potency of inhibitors with a substituted enolpyruvyl group has been attributed to a change in the binding mode through localized flexibility of the peptide backbone<ref name="2a"/><ref name="5a"/>.

~~Two binding mode at the MbtI active site have been observed based on the structure of the inhibitor.~~

IsochorismateSpecifically, <scene name='69/694235/3rv6_with_vae1/1'>2-hydroxybenzoate-based inhibitors</scene> that contain extended hydrophobic enol ether side chains at C3 in place of the enol-pyruvate side chain found in chorismate and isochorismate.

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<scene name='69/694235/3st6_structure_bindingpocket/1'>TextToBeDisplayed</scene>

</StructureSection>

== References ==

Sandbox Reserved 1068: Difference between revisions

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@@ Line 70: / Line 70: @@
 ==Inhibition Studies==
-MbtI Inhibition studies aid in the future design of [http://psychology.wikia.com/wiki/Antitubercular_drugs anti-tubercular agents] and [http://en.wikipedia.org/wiki/Broad-spectrum_antibiotic broad-spectrum antibiotics] with a novel mode of action.  Mimics of the enzyme-bound intermediate of MbtI, <scene name='69/694235/3sr6_inhibitor/3'>isochorismate</scene>, prove to be significantly more potent inhibitors than mimics of the substrate, chorismate <ref name= "1a"/>. The isochorismate mimic based on a 2,3-dihydroxybenzoate scaffold showed low-micromolar inhibition constants against MbtI that were an order of magnitude more potents than the natural substrates. The most potent inhibitors contained hydrophobic enol ether side chains at C3 instead of the enol-pyruvyl side chains seen in chorismate and isochorismate. <ref name="1a">PMID:20512795</ref> Increased potency of inhibitors with a substituted enolpyruvyl group has been attributed to a change in the binding mode through localized flexibility of the peptide backbone.
+MbtI Inhibition studies aid in the future design of [http://psychology.wikia.com/wiki/Antitubercular_drugs anti-tubercular agents] and [http://en.wikipedia.org/wiki/Broad-spectrum_antibiotic broad-spectrum antibiotics] with a novel mode of action.  Mimics of the enzyme-bound intermediate of MbtI, <scene name='69/694235/3sr6_inhibitor/3'>isochorismate</scene>, prove to be significantly more potent inhibitors than mimics of the substrate, chorismate <ref name= "1a"/><ref name="2a"/><ref name="5a"/>. The isochorismate mimic based on a 2,3-dihydroxybenzoate scaffold showed low-micromolar inhibition constants against MbtI that were an order of magnitude more potents than the natural substrates<ref name="2a"/>. The most potent inhibitors contained hydrophobic enol ether side chains at C3 instead of the enol-pyruvyl side chains seen in chorismate and isochorismate. <ref name="1a">PMID:20512795</ref> Increased potency of inhibitors with a substituted enolpyruvyl group has been attributed to a change in the binding mode through localized flexibility of the peptide backbone<ref name="2a"/><ref name="5a"/>.
-Two binding mode at the MbtI active site have been observed based on the structure of the inhibitor.
 IsochorismateSpecifically, <scene name='69/694235/3rv6_with_vae1/1'>2-hydroxybenzoate-based inhibitors</scene> that contain extended hydrophobic enol ether side chains at C3 in place of the enol-pyruvate side chain found in chorismate and isochorismate.
@@ Line 83: / Line 81: @@
 <scene name='69/694235/3st6_structure_bindingpocket/1'>TextToBeDisplayed</scene>
 </StructureSection>
 == References ==
 {{reflist}}