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Structural mechanism of allosteric substrate specificity regulation in a ribonucleotide reductase

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Author

  • K-M Larsson
  • A Jordan
  • R Eliasson
  • P Reichard
  • Derek Logan
  • P Nordlund

Summary, in English

Ribonucleotide reductases (RNRs) catalyze the reduction of ribonucleotides into deoxyribonucleotides, which constitute the precursor pools used for DNA synthesis and repair. Imbalances in these pools increase mutational rates and are detrimental to the cell. Balanced precursor pools are maintained primarily through the regulation of the RNR substrate specificity. Here, the molecular mechanism of the allosteric substrate specificity regulation is revealed through the structures of a dimeric coenzyme B12-dependent RNR from Thermotoga maritima, both in complexes with four effector-substrate nucleotide pairs and in three complexes with only effector. The mechanism is based on the flexibility of loop 2, a key structural element, which forms a bridge between the specificity effector and substrate nucleotides. Substrate specificity is achieved as different effectors and their cognate substrates stabilize specific discrete loop 2 conformations. The mechanism of substrate specificity regulation is probably general for most class I and class II RNRs.

Publishing year

2004

Language

English

Pages

1142-1149

Publication/Series

Nature Structural & Molecular Biology

Volume

11

Issue

11

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Biological Sciences

Status

Published

ISBN/ISSN/Other

  • ISSN: 1545-9985