Novel ATP-cone-driven allosteric regulation of ribonucleotide reductase via the radical-generating subunit

Inna Rozman Grinberg, Daniel Lundin, Mahmudul Hasan, Mikael Crona, Venkateswara Rao Jonna, Christoph Loderer, Margareta Sahlin, Natalia Markova, Ilya Borovok, Gustav Berggren, Anders Hofer, Derek T. Logan, Britt Marie Sjöberg

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Ribonucleotide reductases (RNRs) are key enzymes in DNA metabolism, with allosteric mechanisms controlling substrate specificity and overall activity. In RNRs, the activity master- switch, the ATP-cone, has been found exclusively in the catalytic subunit. In two class I RNR subclasses whose catalytic subunit lacks the ATP-cone, we discovered ATP-cones in the radical- generating subunit. The ATP-cone in the Leeuwenhoekiella blandensis radical-generating subunit regulates activity via quaternary structure induced by binding of nucleotides. ATP induces enzymatically competent dimers, whereas dATP induces non-productive tetramers, resulting in different holoenzymes. The tetramer forms by interactions between ATP-cones, shown by a 2.45 Å crystal structure. We also present evidence for an MnIIIMnIV metal center. In summary, lack of an ATP-cone domain in the catalytic subunit was compensated by transfer of the domain to the radical-generating subunit. To our knowledge, this represents the first observation of transfer of an allosteric domain between components of the same enzyme complex.

Original languageEnglish
Article numbere31529
StatePublished - 1 Feb 2018


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