scholarly journals Glutamate 350 Plays an Essential Role in Conformational Gating of Long-Range Radical Transport inEscherichia coliClass Ia Ribonucleotide Reductase

Biochemistry ◽  
2017 ◽  
Vol 56 (6) ◽  
pp. 856-868 ◽  
Author(s):  
Kanchana Ravichandran ◽  
Ellen C. Minnihan ◽  
Qinghui Lin ◽  
Kenichi Yokoyama ◽  
Alexander T. Taguchi ◽  
...  
Keyword(s):  
Long Range ◽  
Ribonucleotide Reductase ◽  
Essential Role ◽  
Conformational Gating

scholarly journals Essential role of Tip60-dependent recruitment of ribonucleotide reductase at DNA damage sites in DNA repair during G1 phase

2010 ◽  
Vol 24 (4) ◽  
pp. 333-338 ◽  
Author(s):  
H. Niida ◽  
Y. Katsuno ◽  
M. Sengoku ◽  
M. Shimada ◽  
M. Yukawa ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Ribonucleotide Reductase ◽  
Essential Role ◽  
G1 Phase

scholarly journals An essential role for dNTP homeostasis following CDK-induced replication stress

2018 ◽  
Author(s):  
Chen-Chun Pai ◽  
Kuo-Feng Hsu ◽  
Samuel. C. Durley ◽  
Andrea Keszthelyi ◽  
Stephen E. Kearsey ◽  
...  
Keyword(s):  
Ribonucleotide Reductase ◽  
Essential Role ◽  
Genome Instability ◽  
Supply And Demand ◽  
Replication Stress ◽  
Dna Integrity ◽  
Demand Model ◽  
Synthetic Lethal ◽  
Supply And Demand Model ◽  
Important Therapeutic Target

AbstractReplication stress is a common feature of cancer cells, and thus a potentially important therapeutic target. Here we show that CDK-induced replication stress is synthetic lethal with mutations disrupting dNTP homeostasis in fission yeast. Wee1 inactivation leads to increased dNTP demand and replication stress through CDK-induced firing of dormant replication origins. Subsequent dNTP depletion leads to inefficient DNA replication, Mus81-dependent DNA damage, and to genome instability. Cells respond to this replication stress by increasing dNTP supply through Set2-dependent MBF-induced expression of Cdc22, the catalytic subunit of ribonucleotide reductase (RNR). Disrupting dNTP synthesis following Wee1 inactivation, through abrogating Set2-dependent H3K36 tri-methylation or DNA integrity checkpoint inactivation results in critically low dNTP levels, replication collapse and cell death, which can be rescued by increasing dNTP levels. These findings support a ‘dNTP supply and demand’ model in which maintaining dNTP homeostasis is essential to prevent replication catastrophe in response to CDK-induced replication stress.

Radical Initiation in the Class I Ribonucleotide Reductase: Long-Range Proton-Coupled Electron Transfer?

ChemInform ◽  
2003 ◽  
Vol 34 (32) ◽  
Author(s):  
JoAnne Stubbe ◽  
Daniel G. Nocera ◽  
Cyril S. Yee ◽  
Michelle C. Y. Chang
Keyword(s):  
Electron Transfer ◽  
Long Range ◽  
Ribonucleotide Reductase ◽  
Class I ◽  
Radical Initiation ◽  
Proton Coupled Electron Transfer

Long-range proton-coupled electron transfer in the Escherichia coli class Ia ribonucleotide reductase

2017 ◽  
Vol 61 (2) ◽  
pp. 281-292 ◽  
Author(s):  
Steven Y. Reece ◽  
Mohammad R. Seyedsayamdost
Keyword(s):  
Escherichia Coli ◽  
Electron Transfer ◽  
Amino Acid ◽  
Long Range ◽  
Ribonucleotide Reductase ◽  
Unnatural Amino Acids ◽  
Radical Mechanism ◽  
Tyrosyl Radical ◽  
Proton Coupled Electron Transfer ◽  
Vis Spectroscopy

Escherichia coli class Ia ribonucleotide reductase (RNR) catalyzes the conversion of nucleotides to 2′-deoxynucleotides using a radical mechanism. Each turnover requires radical transfer from an assembled diferric tyrosyl radical (Y•) cofactor to the enzyme active site over 35 Å away. This unprecedented reaction occurs via an amino acid radical hopping pathway spanning two protein subunits. To study the mechanism of radical transport in RNR, a suite of biochemical approaches have been developed, such as site-directed incorporation of unnatural amino acids with altered electronic properties and photochemical generation of radical intermediates. The resulting variant RNRs have been investigated using a variety of time-resolved physical techniques, including transient absorption and stopped-flow UV-Vis spectroscopy, as well as rapid freeze-quench EPR, ENDOR, and PELDOR spectroscopic methods. The data suggest that radical transport occurs via proton-coupled electron transfer (PCET) and that the protein structure has evolved to manage the proton and electron transfer co-ordinates in order to prevent ‘off-pathway’ reactivity and build-up of oxidised intermediates. Thus, precise design and control over the factors that govern PCET is key to enabling reversible and long-range charge transport by amino acid radicals in RNR.

Evidence by Site-Directed Mutagenesis Supports Long-Range Electron Transfer in Mouse Ribonucleotide Reductase

Biochemistry ◽  
1995 ◽  
Vol 34 (13) ◽  
pp. 4267-4275 ◽  
Author(s):  
Ulrika Rova ◽  
Karina Goodtzova ◽  
Rolf Ingemarson ◽  
Gity Behravan ◽  
Astrid Graeslund ◽  
...  
Keyword(s):  
Electron Transfer ◽  
Long Range ◽  
Ribonucleotide Reductase ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis

scholarly journals Glutamate 52-β at the α/β subunit interface ofEscherichia coliclass Ia ribonucleotide reductase is essential for conformational gating of radical transfer

2017 ◽  
Vol 292 (22) ◽  
pp. 9229-9239 ◽  
Author(s):  
Qinghui Lin ◽  
Mackenzie J. Parker ◽  
Alexander T. Taguchi ◽  
Kanchana Ravichandran ◽  
Albert Kim ◽  
...  
Keyword(s):  
Ribonucleotide Reductase ◽  
Β Subunit ◽  
Subunit Interface ◽  
Radical Transfer ◽  
Conformational Gating
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