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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/139369
- author
- Larsson, K-M
; Jordan, A
; Eliasson, R
; Reichard, P
; Logan, Derek
LU
and Nordlund, P
- organization
- publishing date
- 2004
- 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
- 2016-04-01 15:35:27
- date last changed
- 2022-02-20 00:03:51
@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}},
doi = {{10.1038/nsmb838}},
volume = {{11}},
year = {{2004}},
}