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Review the kinetic and structural significance of slow-binding enzyme inhibition and evaluate its mechanistic connection to reaction-intermediate and transition-state analogs.

September 1, 1988Accounts of Chemical Research

Significance of slow-binding enzyme inhibition and its relationship to reaction-intermediate analogs

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Authors

JSJohn V. SchlossAmerican University of Health Sciences

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Implication

Biochemical review examines slow-binding enzyme inhibition mechanisms and reaction-intermediate analogs, highlighting structural features that dictate potent, time-dependent enzyme blockade.

Key Points

Review the kinetic and structural significance of slow-binding enzyme inhibition and evaluate its mechanistic connection to reaction-intermediate and transition-state analogs.
Examined theoretical frameworks and kinetic mechanisms underlying slow, tight-binding enzyme inhibition.
Analyzed structural features of enzyme-inhibitor complexes and the chemical properties of reaction-intermediate mimics.
Demonstrated that slow-binding kinetics typically reflect the formation of high-affinity complexes where inhibitors replicate transient reaction intermediates or provoke conformational isomerizations.
Established that reaction-intermediate analogs achieve marked selectivity and extended biological half-lives through exceptionally slow dissociation rates from the enzyme active site.

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John V. Schloss (1988) studied this question.

synapsesocial.com/papers/6a1d292b750575be8d2f3cc2 https://doi.org/10.1021/ar00153a005

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Implication

Biochemical review examines slow-binding enzyme inhibition mechanisms and reaction-intermediate analogs, highlighting structural features that dictate potent, time-dependent enzyme blockade.

Significance of slow-binding enzyme inhibition and its relationship to reaction-intermediate analogs

Discussion

Member takes

Implication

Key Points

Cite This Study

Significance of slow-binding enzyme inhibition and its relationship to reaction-intermediate analogs

Discussion

Member takes

Implication

Key Points

Cite This Study

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