Molecular basis for allosteric specificity regulation in class Ia ribonucleotide reductase from Escherichia coli
Name
Zimanyi-2016-Molecular basis for.pdf
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5.56 MB
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Author(s)
Kang, Gyung Hoon
Chen, Yang-Ting
Zimanyi, Christina Marie
Funk, Michael Andrew
Drennan, Catherine L
Date Issued
January 2016
Journal
eLife
Publisher
eLife Sciences Publications, Ltd.
Citation
Zimanyi, Christina M, Percival Yang-Ting Chen, Gyunghoon Kang, Michael A Funk, and Catherine L Drennan. “Molecular Basis for Allosteric Specificity Regulation in Class Ia Ribonucleotide Reductase from Escherichia Coli.” eLife 5 (January 12, 2016).
Version
Final published version
Abstract
Ribonucleotide reductase (RNR) converts ribonucleotides to deoxyribonucleotides, a reaction that is essential for DNA biosynthesis and repair. This enzyme is responsible for reducing all four ribonucleotide substrates, with specificity regulated by the binding of an effector to a distal allosteric site. In all characterized RNRs, the binding of effector dATP alters the active site to select for pyrimidines over purines, whereas effectors dGTP and TTP select for substrates ADP and GDP, respectively. Here, we have determined structures of Escherichia coli class Ia RNR with all four substrate/specificity effector-pairs bound (CDP/dATP, UDP/dATP, ADP/dGTP, GDP/TTP) that reveal the conformational rearrangements responsible for this remarkable allostery. These structures delineate how RNR ‘reads’ the base of each effector and communicates substrate preference to the active site by forming differential hydrogen bonds, thereby maintaining the proper balance of deoxynucleotides in the cell.
MIT Department
Massachusetts Institute of Technology. Center for Environmental Health Sciences
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
https://doi.org/10.7554/eLife.07141
