Altered conformational sampling along an evolutionary trajectory changes the catalytic activity of an enzyme

Cyclohexadienyl dehydratase (CDT) evolved from a cationic amino acid binding protein ancestor without enzymatic activity (AncCDT-1) via a series of intermediates. Here, the authors combine EPR, X-ray crystallography and MD simulations to study the structural dynamics of these evolutionary intermedia...

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Autores principales: Joe A. Kaczmarski, Mithun C. Mahawaththa, Akiva Feintuch, Ben E. Clifton, Luke A. Adams, Daniella Goldfarb, Gottfried Otting, Colin J. Jackson
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2020
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Acceso en línea:https://doaj.org/article/c19f20f6641e4d50a18da243f7703954
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Sumario:Cyclohexadienyl dehydratase (CDT) evolved from a cationic amino acid binding protein ancestor without enzymatic activity (AncCDT-1) via a series of intermediates. Here, the authors combine EPR, X-ray crystallography and MD simulations to study the structural dynamics of these evolutionary intermediates and observe that they predominantly populate catalytically unproductive conformations, while CDT exclusively samples catalytically relevant compact states, and which reveals how the conformational landscape changes along the evolutionary trajectory.