JoAnne Stubbe

JoAnne Stubbe

Professor Emerita

JoAnne Stubbe studies ribonucleotide reductases — essential enzymes that provide the building blocks for DNA replication, repair and successful targets of multiple clinical drugs.

617-253-1814

Phone

18-581

Office

617-253-0630

Assistant Phone

Education

PhD 1971, University of California, Berkeley

Research Summary

I study ribonucleotide reductases (RNRs), which catalyze the conversion of nucleotides to deoxynucleotides and play an essential role in DNA replication and repair. I support a range of ongoing projects, including those related to the radical propagation pathway utilized by Class I RNRs, the interactions between protein subunits of Class I RNR, the regulation of RNRs, and the mechanisms behind clinical drugs. I also examine the biosynthesis, activation, and regulation of formation of the essential metallo-cofactors of RNRs in E. coli, S. cerevisiae, and humans. JoAnne Stubbe is no longer accepting students.

Awards

  • American Association for the Advancement of Science, Fellow, 2014
  • National Science Foundation, National Medal of Science, 2008
  • National Academy of Sciences, Member, 1992
  • American Academy of Arts and Sciences, Fellow, 1991
  • Welch Award in Chemistry 2010
  • NAS Chemical Sciences Award 2010
  • Pearl Meister Greengard Award 2017

Key Publications

  1. Conformationally Dynamic Radical Transfer within Ribonucleotide Reductase. Greene, BL, Taguchi, AT, Stubbe, J, Nocera, DG. 2017. J. Am. Chem. Soc. 139, 16657-16665.
    doi: 10.1021/jacs.7b08192PMID: 29037038
  2. Spectroscopic Evidence for a H Bond Network at YLocated at the Subunit Interface of Active E. coli Ribonucleotide Reductase. Nick, TU, Ravichandran, KR, Stubbe, J, Kasanmascheff, M, Bennati, M. 2017. Biochemistry 56, 3647-3656.
    doi: 10.1021/acs.biochem.7b00462PMID: 28640584
  3. Glutamate 52-β at the α/β subunit interface ofclass Ia ribonucleotide reductase is essential for conformational gating of radical transfer. Lin, Q, Parker, MJ, Taguchi, AT, Ravichandran, K, Kim, A, Kang, G, Shao, J, Drennan, CL, Stubbe, J. 2017. J. Biol. Chem. 292, 9229-9239.
    doi: 10.1074/jbc.M117.783092PMID: 28377505
  4. Formal Reduction Potentials of Difluorotyrosine and Trifluorotyrosine Protein Residues: Defining the Thermodynamics of Multistep Radical Transfer. Ravichandran, KR, Zong, AB, Taguchi, AT, Nocera, DG, Stubbe, J, Tommos, C. 2017. J. Am. Chem. Soc. 139, 2994-3004.
    doi: 10.1021/jacs.6b11011PMID: 28171730
  5. Glutamate 350 Plays an Essential Role in Conformational Gating of Long-Range Radical Transport in Escherichia coli Class Ia Ribonucleotide Reductase. Ravichandran, K, Minnihan, EC, Lin, Q, Yokoyama, K, Taguchi, AT, Shao, J, Nocera, DG, Stubbe, J. 2017. Biochemistry 56, 856-868.
    doi: 10.1021/acs.biochem.6b01145PMID: 28103007

Recent Publications

  1. 3.3-Å resolution cryo-EM structure of human ribonucleotide reductase with substrate and allosteric regulators bound. Brignole, EJ, Tsai, KL, Chittuluru, J, Li, H, Aye, Y, Penczek, PA, Stubbe, J, Drennan, CL, Asturias, F. 2018. Elife 7, .
    doi: 10.7554/eLife.31502PMID: 29460780
  2. Conformationally Dynamic Radical Transfer within Ribonucleotide Reductase. Greene, BL, Taguchi, AT, Stubbe, J, Nocera, DG. 2017. J. Am. Chem. Soc. 139, 16657-16665.
    doi: 10.1021/jacs.7b08192PMID: 29037038
  3. Spectroscopic Evidence for a H Bond Network at YLocated at the Subunit Interface of Active E. coli Ribonucleotide Reductase. Nick, TU, Ravichandran, KR, Stubbe, J, Kasanmascheff, M, Bennati, M. 2017. Biochemistry 56, 3647-3656.
    doi: 10.1021/acs.biochem.7b00462PMID: 28640584
  4. The diferric-tyrosyl radical cluster of ribonucleotide reductase and cytosolic iron-sulfur clusters have distinct and similar biogenesis requirements. Li, H, Stümpfig, M, Zhang, C, An, X, Stubbe, J, Lill, R, Huang, M. 2017. J. Biol. Chem. 292, 11445-11451.
    doi: 10.1074/jbc.M117.786178PMID: 28515324
  5. Glutamate 52-β at the α/β subunit interface ofclass Ia ribonucleotide reductase is essential for conformational gating of radical transfer. Lin, Q, Parker, MJ, Taguchi, AT, Ravichandran, K, Kim, A, Kang, G, Shao, J, Drennan, CL, Stubbe, J. 2017. J. Biol. Chem. 292, 9229-9239.
    doi: 10.1074/jbc.M117.783092PMID: 28377505
  6. Structure of the Catalytic Domain of the Class I Polyhydroxybutyrate Synthase from Cupriavidus necator. Wittenborn, EC, Jost, M, Wei, Y, Stubbe, J, Drennan, CL. 2016. J. Biol. Chem. 291, 25264-25277.
    doi: 10.1074/jbc.M116.756833PMID: 27742839
  7. Biophysical Characterization of Fluorotyrosine Probes Site-Specifically Incorporated into Enzymes: E. coli Ribonucleotide Reductase As an Example. Oyala, PH, Ravichandran, KR, Funk, MA, Stucky, PA, Stich, TA, Drennan, CL, Britt, RD, Stubbe, J. 2016. J. Am. Chem. Soc. 138, 7951-64.
    doi: 10.1021/jacs.6b03605PMID: 27276098
  8. Photochemical Generation of a Tryptophan Radical within the Subunit Interface of Ribonucleotide Reductase. Olshansky, L, Greene, BL, Finkbeiner, C, Stubbe, J, Nocera, DG. 2016. Biochemistry 55, 3234-40.
    doi: 10.1021/acs.biochem.6b00292PMID: 27159163
  9. Charge-Transfer Dynamics at the α/β Subunit Interface of a Photochemical Ribonucleotide Reductase. Olshansky, L, Stubbe, J, Nocera, DG. 2016. J. Am. Chem. Soc. 138, 1196-205.
    doi: 10.1021/jacs.5b09259PMID: 26710997
  10. Composition and Structure of the Inorganic Core of Relaxed Intermediate X(Y122F) of Escherichia coli Ribonucleotide Reductase. Doan, PE, Shanmugam, M, Stubbe, J, Hoffman, BM. 2015. J. Am. Chem. Soc. 137, 15558-66.
    doi: 10.1021/jacs.5b10763PMID: 26636616
More Publications

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Photo Credit: Justin Knight