Intramolecular epistasis and the evolution of a new enzymatic function

Sajid Noor, Matthew C. Taylor, Robyn J. Russell, Lars S. Jermiin, Colin J. Jackson, John G. Oakeshott, Colin Scott*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)
3 Downloads (Pure)

Abstract

Atrazine chlorohydrolase (AtzA) and its close relative melamine deaminase (TriA) differ by just nine amino acid substitutions but have distinct catalytic activities. Together, they offer an informative model system to study the molecular processes that underpin the emergence of new enzymatic function. Here we have constructed the potential evolutionary trajectories between AtzA and TriA, and characterized the catalytic activities and biophysical properties of the intermediates along those trajectories. The order in which the nine amino acid substitutions that separate the enzymes could be introduced to either enzyme, while maintaining significant catalytic activity, was dictated by epistatic interactions, principally between three amino acids within the active site: namely, S331C, N328D and F84L. The mechanistic basis for the epistatic relationships is consistent with a model for the catalytic mechanisms in which protonation is required for hydrolysis of melamine, but not atrazine.

Original languageEnglish
Article numbere39822
Pages (from-to)1-11
Number of pages11
JournalPLoS ONE
Volume7
Issue number6
DOIs
Publication statusPublished - 29 Jun 2012
Externally publishedYes

Bibliographical note

Copyright Noor et al. 2012. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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