ArticleProceedings of the National Academy of Sciences of the United States of America2006
Alternative mutations of a positively selected residue elicit gain or loss of functionalities in enzyme evolution.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Glutathione Transferases as Efficient Ketosteroid Isomerases.Frontiers in molecular biosciences · 2021Review
- Exploring sequence-function space of a poplar glutathione transferase using designed information-rich gene variants.Protein engineering, design & selection : PEDS · 2017Article
- Comparison of epsilon- and delta-class glutathione S-transferases: the crystal structures of the glutathione S-transferases DmGSTE6 and DmGSTE7 from Drosophila melanogaster.Acta crystallographica. Section D, Biological crystallography · 2015Article
- Evolution in an ancient detoxification pathway is coupled with a transition to herbivory in the drosophilidae.Molecular biology and evolution · 2014Article
- Prediction of substrates for glutathione transferases by covalent docking.Journal of chemical information and modeling · 2014Article
- Cys-X scanning for expansion of active-site residues and modulation of catalytic functions in a glutathione transferase.The Journal of biological chemistry · 2011Article
- Molecular evolution and the role of oxidative stress in the expansion and functional diversification of cytosolic glutathione transferases.BMC evolutionary biology · 2010Article
- Minor modifications of the C-terminal helix reschedule the favored chemical reactions catalyzed by theta class glutathione transferase T1-1.The Journal of biological chemistry · 2010Article
- Phylogenetic analysis of ADP-glucose pyrophosphorylase subunits reveals a role of subunit interfaces in the allosteric properties of the enzyme.Plant physiology · 2009Article
- Force-clamp spectroscopy detects residue co-evolution in enzyme catalysis.The Journal of biological chemistry · 2008Article
- The evolution of catalytic efficiency and substrate promiscuity in human theta class 1-1 glutathione transferase.Journal of molecular biology · 2006Article
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4 authors.
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Abstract
All molecular species in an organism are connected physically and functionally to other molecules. In evolving systems, it is not obvious to what extent functional properties of a protein can change to selective advantage and leave intact favorable traits previously acquired. This uncertainty has particular significance in the evolution of novel pathways for detoxication, because an organism challenged with new xenobiotics in the environment may still require biotransformation of previously encountered toxins. Positive selection has been proposed as an evolutionary mechanism for facile adaptive responses of proteins to changing conditions. Here, we show, by saturation mutagenesis, that mutations of a hypervariable residue in human glutathione transferase M2-2 can differentially change the enzyme's substrate-activity profile with alternative substrates and, furthermore, enable or disable dissimilar chemical reactions. Crystal structures demonstrate that activity with epoxides is enabled through removal of steric hindrance from a methyl group, whereas activities with an orthoquinone and a nitroso donor are maintained in the variant enzymes. Given the diversity of cellular activities in which a single protein can be engaged, the selective transmutation of functional properties has general significance in molecular evolution.
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