scholarly journals A Proton Wire Mediates Proton Coupled Electron Transfer from Hydroxyurea and Other Hydroxamic Acids to Tyrosyl Radical in Class Ia Ribonucleotide Reductase

2020 ◽  
Vol 124 (2) ◽  
pp. 345-354 ◽  
Author(s):  
Adam R. Offenbacher ◽  
Bridgette A. Barry
Keyword(s):  
Electron Transfer ◽  
Ribonucleotide Reductase ◽  
Hydroxamic Acids ◽  
Tyrosyl Radical ◽  
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.

scholarly journals Function of the Diiron Cluster ofEscherichia coliClass Ia Ribonucleotide Reductase in Proton-Coupled Electron Transfer

2013 ◽  
Vol 135 (23) ◽  
pp. 8585-8593 ◽  
Author(s):  
Bigna Wörsdörfer ◽  
Denise A. Conner ◽  
Kenichi Yokoyama ◽  
Jovan Livada ◽  
Mohammad Seyedsayamdost ◽  
...  
Keyword(s):  
Electron Transfer ◽  
Ribonucleotide Reductase ◽  
Proton Coupled Electron Transfer

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

Electron transfer in tyrosyl radical formation in the R2 subunit of mouse ribonucleotide reductase

2003 ◽  
Vol 96 (1) ◽  
pp. 261
Author(s):  
Danny Yun ◽  
Lana Saleh ◽  
J.Martin Bollinger ◽  
Boi Hanh Huynh
Keyword(s):  
Electron Transfer ◽  
Ribonucleotide Reductase ◽  
Radical Formation ◽  
Tyrosyl Radical ◽  
R2 Subunit

scholarly journals Proton-coupled electron transfer: the mechanistic underpinning for radical transport and catalysis in biology

2006 ◽  
Vol 361 (1472) ◽  
pp. 1351-1364 ◽  
Author(s):  
Steven Y Reece ◽  
Justin M Hodgkiss ◽  
JoAnne Stubbe ◽  
Daniel G Nocera
Keyword(s):  
Electron Transfer ◽  
Amino Acid ◽  
Active Sites ◽  
Bond Activation ◽  
Mechanical Effect ◽  
Model Systems ◽  
Tyrosyl Radical ◽  
Quantum Mechanical Effect ◽  
Proton Coupled Electron Transfer ◽  
Amino Acid Radicals

Charge transport and catalysis in enzymes often rely on amino acid radicals as intermediates. The generation and transport of these radicals are synonymous with proton-coupled electron transfer (PCET), which intrinsically is a quantum mechanical effect as both the electron and proton tunnel. The caveat to PCET is that proton transfer (PT) is fundamentally limited to short distances relative to electron transfer (ET). This predicament is resolved in biology by the evolution of enzymes to control PT and ET coordinates on highly different length scales. In doing so, the enzyme imparts exquisite thermodynamic and kinetic controls over radical transport and radical-based catalysis at cofactor active sites. This discussion will present model systems containing orthogonal ET and PT pathways, thereby allowing the proton and electron tunnelling events to be disentangled. Against this mechanistic backdrop, PCET catalysis of oxygen–oxygen bond activation by mono-oxygenases is captured at biomimetic porphyrin redox platforms. The discussion concludes with the case study of radical-based quantum catalysis in a natural biological enzyme, class I Escherichia coli ribonucleotide reductase. Studies are presented that show the enzyme utilizes both collinear and orthogonal PCET to transport charge from an assembled diiron-tyrosyl radical cofactor to the active site over 35 Å away via an amino acid radical-hopping pathway spanning two protein subunits.

scholarly journals Redox-Linked Conformational Control of Proton-Coupled Electron Transfer: Y122 in the Ribonucleotide Reductase β2 Subunit

2013 ◽  
Vol 117 (28) ◽  
pp. 8457-8468 ◽  
Author(s):  
Adam R. Offenbacher ◽  
Lori A. Burns ◽  
C. David Sherrill ◽  
Bridgette A. Barry
Keyword(s):  
Electron Transfer ◽  
Ribonucleotide Reductase ◽  
Conformational Control ◽  
Proton Coupled Electron Transfer
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