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

TitleLong-range proton-coupled electron transfer in the class Ia ribonucleotide reductase.
Publication TypeJournal Article
Year of Publication2017
AuthorsReece, SY, Seyedsayamdost, MR
JournalEssays Biochem
Date Published2017 05 09
KeywordsElectron Transport, Escherichia coli, Escherichia coli Proteins, Metalloproteins, Ribonucleotide Reductases

<p> 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.</p>

Alternate JournalEssays Biochem
PubMed ID28487404
Grant ListGM098299 / GM / NIGMS NIH HHS / United States