Skip to main content
OSTI.GOVU.S. Department of Energy Office of Scientific and Technical Information
U.S. Department of Energy
Office of Scientific and Technical Information
 

Structure of a ribonucleotide reductase R2 protein radical

Journal Article · · Science
 [1];  [2];  [2];  [3];  [2];  [2];  [4];  [4];  [2];  [4];  [4];  [4];  [4];  [4];  [5];  [5];  [5];  [6];  [6];  [6] more »;  [4];  [4];  [4];  [2];  [2];  [4];  [7];  [2] « less
  1. Stockholm Univ. (Sweden); Univ. of Toulouse (France); Centre National de la Recherche Scientifique (CNRS) (France)
  2. Stockholm Univ. (Sweden); Arrhenius Laboratories for Natural Sciences, Stockholm (Sweden)
  3. Stockholm Univ. (Sweden); Arrhenius Laboratories for Natural Sciences, Stockholm (Sweden); Lund Univ. (Sweden)
  4. Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
  5. Science and Technology Facilities Council (STFC), Oxford (United Kingdom). Diamond Light Source, Ltd.
  6. SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States). Linac Coherent Light Source (LCLS)
  7. Uppsala Univ. (Sweden); Sprint Bioscience, Huddinge (Sweden)
+ Show Author Affiliations
Aerobic ribonucleotide reductases (RNRs) initiate synthesis of DNA building blocks by generating a free radical within the R2 subunit; the radical is subsequently shuttled to the catalytic R1 subunit through proton-coupled electron transfer (PCET). Here we present a high-resolution room temperature structure of the class Ie R2 protein radical captured by x-ray free electron laser serial femtosecond crystallography. The structure reveals conformational reorganization to shield the radical and connect it to the translocation path, with structural changes propagating to the surface where the protein interacts with the catalytic R1 subunit. Restructuring of the hydrogen bond network, including a notably short O–O interaction of 2.41 angstroms, likely tunes and gates the radical during PCET. These structural results help explain radical handling and mobilization in RNR and have general implications for radical transfer in proteins.
Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). National Energy Research Scientific Computing Center (NERSC); SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States). Linac Coherent Light Source (LCLS)
Sponsoring Organization:
National Institutes of Health (NIH); USDOE Office of Science (SC), Biological and Environmental Research (BER)
Grant/Contract Number:
AC02-05CH11231; AC02-76SF00515
OSTI ID:
2439705
Journal Information:
Science, Journal Name: Science Journal Issue: 6666 Vol. 382; ISSN 0036-8075
Publisher:
AAASCopyright Statement
Country of Publication:
United States
Language:
English

References (58)

MolProbity: More and better reference data for improved all-atom structure validation: PROTEIN SCIENCE.ORG journal November 2017
Hydroxyurea and hydroxamic acid derivatives as antitumor drugs journal April 2009
Redox-induced structural changes in the di-iron and di-manganese forms of Bacillus anthracis ribonucleotide reductase subunit NrdF suggest a mechanism for gating of radical access journal August 2019
Electron Spin Resonance of the Iron-containing Protein B2 from Ribonucleotide Reductase journal June 1972
Orientation of the Tyrosyl Radical in Salmonella typhimurium Class Ib Ribonucleotide Reductase Determined by High Field EPR of R2F Single Crystals journal October 2006
Crystal structure of reduced protein R2 of ribonucleotide reductase: the structural basis for oxygen activation at a dinuclear iron site journal September 1996
Low barrier hydrogen bonds in protein structure and function journal January 2021
Evolutionary Origin of a Secondary Structure: π-Helices as Cryptic but Widespread Insertional Variations of α-Helices That Enhance Protein Functionality journal November 2010
Are Short, Low-Barrier Hydrogen Bonds Unusually Strong? journal December 2010
Crystal Structure of the Di-iron/Radical Protein of Ribonucleotide Reductase from Corynebacterium ammoniagenes, journal December 2001
Structure of Salmonella typhimurium nrdF Ribonucleotide Reductase in Its Oxidized and Reduced Forms † , ‡ journal September 1998
Radical Initiation in the Class I Ribonucleotide Reductase:  Long-Range Proton-Coupled Electron Transfer? journal June 2003
Biochemistry and Theory of Proton-Coupled Electron Transfer journal January 2014
A Tyrosyl−Dimanganese Coupled Spin System is the Native Metalloradical Cofactor of the R2F Subunit of the Ribonucleotide Reductase of Corynebacterium ammoniagenes journal August 2010
A Hot Oxidant, 3-NO 2 Y 122 Radical, Unmasks Conformational Gating in Ribonucleotide Reductase journal November 2010
Function of the Diiron Cluster of Escherichia coli Class Ia Ribonucleotide Reductase in Proton-Coupled Electron Transfer journal May 2013
Redox-Linked Structural Changes in Ribonucleotide Reductase journal May 2009
Radicals in Biology: Your Life Is in Their Hands journal August 2021
Ligand-Induced Proton Transfer and Low-Barrier Hydrogen Bond Revealed by X-ray Crystallography journal June 2015
Redox-Linked Conformational Control of Proton-Coupled Electron Transfer: Y122 in the Ribonucleotide Reductase β2 Subunit journal July 2013
Hydrogen Atom Transfer in Ribonucleotide Reductase (RNR) journal November 1998
Proton-Coupled Electron Transfer and Redox-Active Tyrosines: Structure and Function of the Tyrosyl Radicals in Ribonucleotide Reductase and Photosystem II journal February 2012
Three-dimensional structure of the free radical protein of ribonucleotide reductase journal June 1990
Femtosecond X-ray protein nanocrystallography journal February 2011
Accurate macromolecular structures using minimal measurements from X-ray free-electron lasers journal March 2014
CHARMM36m: an improved force field for folded and intrinsically disordered proteins journal November 2016
Drop-on-demand sample delivery for studying biocatalysts in action at X-ray free-electron lasers journal February 2017
Metal-free ribonucleotide reduction powered by a DOPA radical in Mycoplasma pathogens journal October 2018
Metallation and mismetallation of iron and manganese proteins in vitro and in vivo: the class I ribonucleotide reductases as a case study journal January 2012
Long-range proton-coupled electron transfer in the Escherichia coli class Ia ribonucleotide reductase journal May 2017
Scalable molecular dynamics on CPU and GPU architectures with NAMD journal July 2020
Efficient growth inhibition of Bacillus anthracis by knocking out the ribonucleotide reductase tyrosyl radical journal December 2005
Displacement of the tyrosyl radical cofactor in ribonucleotide reductase obtained by single-crystal high-field EPR and 1.4-A x-ray data journal March 2003
Generation of a stable, aminotyrosyl radical-induced  2 2 complex of Escherichia coli class Ia ribonucleotide reductase journal February 2013
Protein structural ensembles are revealed by redefining X-ray electron density noise journal December 2013
Metal-free class Ie ribonucleotide reductase from pathogens initiates catalysis with a tyrosine-derived dihydroxyphenylalanine radical journal September 2018
Residues Important for Radical Stability in Ribonucleotide Reductase from Escherichia coli journal March 1995
Use of Structural Phylogenetic Networks for Classification of the Ferritin-like Superfamily journal June 2012
Rapid X-ray Photoreduction of Dimetal-Oxygen Cofactors in Ribonucleotide Reductase journal February 2013
Crystal Structural Studies of Changes in the Native Dinuclear Iron Center of Ribonucleotide Reductase Protein R2 from Mouse journal November 2004
Phaser crystallographic software journal July 2007
XDS journal January 2010
Features and development of Coot journal March 2010
Radiation damage in macromolecular crystallography: what is it and why should we care? journal March 2010
Towards automated crystallographic structure refinement with phenix.refine journal March 2012
Data Exploration Toolkit for serial diffraction experiments journal January 2015
Online_DPI : a web server to calculate the diffraction precision index for a protein structure journal April 2015
XFEL diffraction: developing processing methods to optimize data quality journal January 2015
The Macromolecular Femtosecond Crystallography Instrument at the Linac Coherent Light Source journal February 2019
Do we see what we should see? Describing non-covalent interactions in protein structures including precision journal December 2013
Improving signal strength in serial crystallography with DIALS geometry refinement journal September 2018
Macromolecular structure determination using X-rays, neutrons and electrons: recent developments in Phenix journal October 2019
Structural Basis for Activation of Class Ib Ribonucleotide Reductase journal August 2010
Structure of a trapped radical transfer pathway within a ribonucleotide reductase holocomplex journal March 2020
Ribonucleotide Reductases: Structure, Chemistry, and Metabolism Suggest New Therapeutic Targets journal June 2020
“Strong” Hydrogen Bonds in Chemistry and Biology journal October 1997
HOLLOW: Generating Accurate Representations of Channel and Interior Surfaces in Molecular Structures journal January 2008
Redox-controlled reorganization and flavin strain within the ribonucleotide reductase R2b–NrdI complex monitored by serial femtosecond crystallography journal September 2022

Similar Records

A stable Fe{sup III}-Fe{sup IV} replacement of tyrosyl radical in a class I ribonucleotide reductase
Journal Article · Fri May 20 00:00:00 EDT 2005 · Biochemical and Biophysical Research Communications · OSTI ID:20709197
Structures of the Yeast Ribonucleotide Reductase Rnr2 and Rnr4 Homodimers
Journal Article · Sun Mar 07 23:00:00 EST 2010 · Biochemistry-US · OSTI ID:1008708
Structures of Class Id Ribonucleotide Reductase Catalytic Subunits Reveal a Minimal Architecture for Deoxynucleotide Biosynthesis
Journal Article · Sun Mar 10 20:00:00 EDT 2019 · Biochemistry · OSTI ID:1544859

Related Subjects

59 BASIC BIOLOGICAL SCIENCES