Abstract
Previously it was found that 4-hydroxybenzaldehyde is a competitive inhibitor of GABA transaminase. Here 3-chloro-1-(4-hydroxyphenyl)propan-1-one (9), a 4-hydroxybenzaldehyde analogue, was found to inactivate potently the enzyme in a time-dependent manner. alpha-Ketoglutarate prevented the enzyme from inactivation, suggesting that the inactivation occurs in its active site. Several experiments indicated that the inactivation is irreversible. This study provides a novel strategy for the design of more effective inhibitors.
MeSH terms
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4-Aminobutyrate Transaminase / antagonists & inhibitors*
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4-Aminobutyrate Transaminase / chemistry*
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Catalytic Domain
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Chemistry, Pharmaceutical / methods*
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Dose-Response Relationship, Drug
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Drug Design
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Enzyme Activation
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / pharmacology*
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Humans
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Ketoglutaric Acids / chemistry*
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Kinetics
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Models, Chemical
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Propiophenones / chemical synthesis
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Propiophenones / chemistry*
Substances
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3-chloro-1-(4-hydroxyphenyl)propan-1-one
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Enzyme Inhibitors
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Ketoglutaric Acids
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Propiophenones
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4-Aminobutyrate Transaminase