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Updated: Jun 15, 2026

Computational Prediction of Amino Acid Preferences of Potentially Multispecific Peptide-Binding Domains Involved in Protein-Protein Interactions

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Published on: January 26, 2024

Enzyme promiscuity: a mechanistic and evolutionary perspective.

Olga Khersonsky¹, Dan S Tawfik

¹Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel.

Annual Review of Biochemistry

|March 19, 2010

Summary

Enzymes often catalyze unintended reactions, a phenomenon called promiscuity. This infidelity in molecular recognition has significant structural, mechanistic, and evolutionary implications for enzyme function and adaptation.

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Area of Science:

Biochemistry
Molecular Biology
Evolutionary Biology

Background:

Most enzymes exhibit high specificity for their evolved substrates.
Enzyme promiscuity, the ability to catalyze reactions beyond their primary function, is a widespread phenomenon.

Purpose of the Study:

To explore the structural, mechanistic, and evolutionary consequences of enzyme promiscuity.
To define enzyme promiscuity and discuss its generality and physiological relevance.

Main Methods:

Review of existing literature on enzyme promiscuity.
Analysis of mechanistic enzymology principles.
Discussion of evolutionary hypotheses related to enzyme function.

Main Results:

Enzyme promiscuity is a common feature across many enzymes.
Mechanistic insights reveal how enzymes can accommodate non-native reactions.
Promiscuous activities are proposed as evolutionary starting points for new enzyme functions.

Conclusions:

Enzyme promiscuity challenges the notion of absolute enzymatic specificity.
Understanding promiscuity is key to comprehending enzyme evolution and adaptation.
Promiscuous activities offer a substrate for evolutionary innovation in enzymes.