Redox-Linked Structural Changes in Ribonucleotide Reductase

摘要

Ribonucleotide reductase (RNR) catalyzes the reduction of ribonucleotides to deoxyribonucleotides. Class I RNRs are composed of a 1:1 complex of two homodimeric proteins, α2 and β2. α2 contains the binding site for substrates and allosteric effectors that govern turnover rate and specificity, and β2 houses the essential diferric-tyrosyl radical (residue 122, Y122·) cofactor.Y122· acts as a radical initiator, generating a thiyl radical in α2, ～35 A removed. Long distance proton coupled electron transfer (PCET) is facilitated by a series of amino acid radical intermediates, which serve to accelerate the reaction rate into a physiologically relevant range.rnIn this work, vibrational spectroscopy is used to show that electron transfer to and from the tyrosyl radical (Y122·) in RNR is coupled to a conformational change in the β2 subunit. Such redox-linked conformational changes are important because they can modulate the interaction of Y122 with its hydrogen bonding partner and provide local, structural control of its PCET reactions.