Abstract
Anthranilate synthase catalyses the conversion of chorismate to anthranilate, a key step in tryptophan biosynthesis. A series of 3-(1-carboxy-ethoxy) benzoic acids were synthesised as chorismate analogues, with varying functionality at C-4, the position of the departing hydroxyl group in chorismate. Most of the compounds were moderate inhibitors of anthranilate synthase, with inhibition constants between 20-30 microM. The exception was 3-(1-carboxy-ethoxy) benzoic acid, (C-4 = H), for which K(I)= 2.4 microM. These results suggest that a hydrogen bonding interaction with the active site general acid (Glu309) is less important than previously assumed for inhibition of the enzyme by these aromatic chorismate analogues.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anthranilate Synthase / antagonists & inhibitors*
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Anthranilate Synthase / chemistry
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Benzoates / chemical synthesis*
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Benzoates / chemistry
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Benzoates / pharmacology*
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Binding Sites
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Chorismic Acid / analogs & derivatives
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Chorismic Acid / chemical synthesis
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Chorismic Acid / chemistry
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Enzyme Activation / drug effects
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Hydrogen Bonding
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Models, Molecular
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Molecular Structure
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Serratia marcescens / drug effects
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Serratia marcescens / enzymology
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Benzoates
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Enzyme Inhibitors
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Anthranilate Synthase
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Chorismic Acid