Photochemical Rescue of a Conformationally Inactivated Ribonucleotide Reductase

Photochemical Generation of a Tryptophan Radical within the Subunit Interface of Ribonucleotide Reductase.

The Escherichia coli class Ia ribonucleotide reductase (RNR) achieves forward and reverse proton-coupled electron transfer (PCET) over a pathway of redox active amino acids (β-Y122 ⇌ β-Y356 ⇌ α-Y731 ⇌ α-Y730 ⇌ α-C439) spanning ∼35 Å and two subunits every time it turns over. We have developed photoRNRs that allow radical transport to be phototriggered at tyrosine (Y) or fluorotyrosine (FnY) res...

Tangled up in knots: structures of inactivated forms of E. coli class Ia ribonucleotide reductase.

Ribonucleotide reductases (RNRs) provide the precursors for DNA biosynthesis and repair and are successful targets for anticancer drugs such as clofarabine and gemcitabine. Recently, we reported that dATP inhibits E. coli class Ia RNR by driving formation of RNR subunits into α4β4 rings. Here, we present the first X-ray structure of a gemcitabine-inhibited E. coli RNR and show that the previous...

Photochemical Ribonucleotide Reductase for the Study of Proton-Coupled Electron Transfer

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 ...

Re(bpy)(CO)[subscript 3]CN as a Probe of Conformational Flexibility in a Photochemical Ribonucleotide Reductase

Photochemical ribonucleotide reductases (photoRNRs) have been developed to study the protoncoupled electron transfer (PCET) mechanism of radical transport in class I E. coli ribonucleotide reductase (RNR). The transport of the effective radical occurs along several conserved aromatic residues across two subunits: β2(•Y122→W48→Y356)→ α2(Y731→Y730→C439). The current model for RNR activity suggest...

Ribonucleotide reductase in developing brain.