Abstract
3-(2-Carboxyethyl)-4,6-dichloro-1H-indole-2-carboxylic acid (MDL-29951), an antagonist of the glycine site of the NMDA receptor, has been found to be an allosteric inhibitor of the enzyme fructose 1,6-bisphosphatase. The compound binds at the AMP regulatory site by X-ray crystallography. This represents a new approach to inhibition of fructose 1,6-bisphosphatase and serves as a lead for further drug design.
MeSH terms
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Adenosine Monophosphate / metabolism*
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Allosteric Site
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Animals
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Crystallography, X-Ray
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / metabolism
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Enzyme Inhibitors / pharmacology
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Fructose-Bisphosphatase / antagonists & inhibitors*
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Fructose-Bisphosphatase / metabolism
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Humans
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Indoles / chemistry
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Indoles / metabolism*
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Indoles / pharmacology*
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Models, Molecular
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Propionates / chemistry
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Propionates / metabolism*
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Propionates / pharmacology*
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Rabbits
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Rats
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Recombinant Proteins / antagonists & inhibitors
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Recombinant Proteins / metabolism
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Structure-Activity Relationship
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Swine
Substances
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2-carboxy-4,6-dichloro-(1H)-indole-3-propanoic acid
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Enzyme Inhibitors
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Indoles
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Propionates
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Recombinant Proteins
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Adenosine Monophosphate
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Fructose-Bisphosphatase