Redox-Linked Changes to the Hydrogen-Bonding Network of Ribonucleotide Reductase β2
Name
Stubbe_Redox-linked.pdf
Size
1.34 MB
Format
Adobe PDF
Checksum (MD5)
bed258d8813099af0350f8b3c46121c7
Author(s)
Offenbacher, Adam R.
Minnihan, Ellen Catherine
Stubbe, JoAnne
Barry, Bridgette A.
Date Issued
April 2013
Journal
Journal of the American Chemical Society
Publisher
American Chemical Society (ACS)
Citation
Offenbacher, Adam R., Ellen C. Minnihan, JoAnne Stubbe, and Bridgette A. Barry. “Redox-Linked Changes to the Hydrogen-Bonding Network of Ribonucleotide Reductase Β2.” Journal of the American Chemical Society 135, no. 17 (May 2013): 6380–6383.
Version
Author's final manuscript
Abstract
Ribonucleotide reductase (RNR) catalyzes conversion of nucleoside diphosphates (NDPs) to 2′-deoxynucleotides, a critical step in DNA replication and repair in all organisms. Class-Ia RNRs, found in aerobic bacteria and all eukaryotes, are a complex of two subunits: α2 and β2. The β2 subunit contains an essential diferric–tyrosyl radical (Y122O•) cofactor that is needed to initiate reduction of NDPs in the α2 subunit. In this work, we investigated the Y122O• reduction mechanism in Escherichia coli β2 by hydroxyurea (HU), a radical scavenger and cancer therapeutic agent. We tested the hypothesis that Y122OH redox reactions cause structural changes in the diferric cluster. Reduction of Y122O• was studied using reaction-induced FT-IR spectroscopy and [[superscript 13]C]aspartate-labeled β2. These Y122O• minus Y122OH difference spectra provide evidence that the Y122OH redox reaction is associated with a frequency change to the asymmetric vibration of D84, a unidentate ligand to the diferric cluster. The results are consistent with a redox-induced shift in H-bonding between Y122OH and D84 that may regulate proton-transfer reactions on the HU-mediated inactivation pathway in isolated β2.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Chemistry
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1021/ja3032949
