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

Rozman Grinberg, Inna; Lundin, Daniel; Hasan, Mahmudul LU ; Crona, Mikael; Jonna, Venkateswara Rao; Loderer, Christoph; Sahlin, Margareta; Markova, Natalia LU ; Borovok, Ilya and Berggren, Gustav, et al. (2018) In eLife 7.
Abstract

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... (More)

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.

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eLife
volume
7
publisher
eLife Sciences Publications LTD.
external identifiers
  • scopus:85043531178
ISSN
2050-084X
DOI
10.7554/eLife.31529
language
English
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yes
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1996e8d2-e4b2-4d0b-9e29-99584aa843a1
date added to LUP
2018-03-21 13:46:45
date last changed
2018-08-12 04:43:12
@article{1996e8d2-e4b2-4d0b-9e29-99584aa843a1,
  abstract     = {<p>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.</p>},
  articleno    = {e31529},
  author       = {Rozman Grinberg, Inna and Lundin, Daniel and Hasan, Mahmudul and Crona, Mikael and Jonna, Venkateswara Rao and Loderer, Christoph and Sahlin, Margareta and Markova, Natalia and Borovok, Ilya and Berggren, Gustav and Hofer, Anders and Logan, Derek T. and Sjöberg, Britt Marie},
  issn         = {2050-084X},
  language     = {eng},
  month        = {02},
  publisher    = {eLife Sciences Publications LTD.},
  series       = {eLife},
  title        = {Novel ATP-cone-driven allosteric regulation of ribonucleotide reductase via the radical-generating subunit},
  url          = {http://dx.doi.org/10.7554/eLife.31529},
  volume       = {7},
  year         = {2018},
}