Enzyme promiscuity: A mechanistic and evolutionary perspective

Tawfik, Olga Khersonsky and Dan S.

doi:10.1146/annurev-biochem-030409-143718

Cited by 1,355Protein Structure and DynamicsEvolution and Genetic DynamicsEnzyme Structure and Function

Enzyme promiscuity: A mechanistic and evolutionary perspective

Tawfik, Olga Khersonsky and Dan S.·2010·Annual Review of Biochemistry

DOI 10.1146/annurev-biochem-030409-143718

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Abstract

Many, if not most, enzymes can promiscuously catalyze reactions, or act on substrates, other than those for which they evolved. Here, we discuss the structural, mechanistic, and evolutionary implications of this manifestation of infidelity of molecular recognition. We define promiscuity and related phenomena and also address their generality and physiological implications. We discuss the mechanistic enzymology of promiscuity—how enzymes, which generally exert exquisite specificity, catalyze other, and sometimes barely related, reactions. Finally, we address the hypothesis that promiscuous enzymatic activities serve as evolutionary starting points and highlight the unique evolutionary features of promiscuous enzyme functions.

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“Such environmental or geological changes could also have led to innovation of increasingly specific and functional catalysts from the initially diverse and chaotic prebiotic milieu [91,92].”
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Mechanistic Insights into the Isochorismate Pyruvate Lyase Activity of the Catalytically Promiscuous PchB from Combinatorial Mutagenesis and Selection
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A large-scale evaluation of computational protein function prediction
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Authors: Tawfik, O. K. A. D. S.
Affiliations: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel;
Venue: Annual Review of Biochemistry
Publisher: Annual Reviews
Published: 2010-06-07
Volume: 79
Issue: 1
Pages: 471-505
ISSN: 0066-4154 (ISSN-L)
1545-4509
DOI: 10.1146/annurev-biochem-030409-143718
OpenAlex: W2128312954
Cited by: 1,355
References: 198
Citations by year: 2026: 74 · 2025: 70 · 2024: 75 · 2023: 78 · 2022: 94 · 2021: 91 · 2020: 91 · 2019: 96 · 2018: 87 · 2017: 95 · 2016: 76 · 2015: 98 · 2014: 96 · 2013: 81 · 2012: 71
FWCI: 6.44
Type: journal article
Language: en
Open access: closed
Locations: Annual Review of Biochemistry (publishedVersion)
PubMed (publishedVersion)
Funders: European Commission
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
Keywords: enzyme promiscuity, enzyme evolution, molecular recognition, substrate specificity, enzyme mechanism
MeSH terms: Catalysis, Enzymes, Humans, Substrate Specificity, Evolution, Molecular, Catalytic Domain

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Enzyme promiscuity: A mechanistic and evolutionary perspective

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