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Structural mechanism of allosteric substrate specificity regulation in a ribonucleotide reductase

Larsson, K-M; Jordan, A; Eliasson, R; Reichard, P; Logan, Derek LU and Nordlund, P (2004) In Nature Structural & Molecular Biology 11(11). p.1142-1149
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Structural & Molecular Biology
volume
11
issue
11
pages
1142 - 1149
publisher
Nature Publishing Group
external identifiers
  • pmid:15475969
  • wos:000224847600026
  • scopus:7544227865
ISSN
1545-9985
DOI
10.1038/nsmb838
language
English
LU publication?
yes
id
3c3e81a4-b8bc-4288-95ac-f5de4d0ceb11 (old id 139369)
date added to LUP
2007-07-09 15:47:54
date last changed
2017-12-10 04:26:21
@article{3c3e81a4-b8bc-4288-95ac-f5de4d0ceb11,
  abstract     = {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.},
  author       = {Larsson, K-M and Jordan, A and Eliasson, R and Reichard, P and Logan, Derek and Nordlund, P},
  issn         = {1545-9985},
  language     = {eng},
  number       = {11},
  pages        = {1142--1149},
  publisher    = {Nature Publishing Group},
  series       = {Nature Structural & Molecular Biology},
  title        = {Structural mechanism of allosteric substrate specificity regulation in a ribonucleotide reductase},
  url          = {http://dx.doi.org/10.1038/nsmb838},
  volume       = {11},
  year         = {2004},
}