JoAnne Stubbe

JoAnne Stubbe

Professor Emerita

Before closing her lab, JoAnne Stubbe studied 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
  • BA, 1968, Chemistry, University of Pennsylvania

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

  • Priestley Medalist, American Chemical Society, 2020
  • 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 Y356 Located 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 of Escherichia coli class 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. Disulfide radical anion as a super-reductant in biology and photoredox chemistry. Zhu, Q, Costentin, C, Stubbe, J, Nocera, DG. 2023. Chem Sci 14, 6876-6881.
    doi: 10.1039/d3sc01867aPMID:37389245
  2. Radical Transport Facilitated by a Proton Transfer Network at the Subunit Interface of Ribonucleotide Reductase. Cui, C, Song, DY, Drennan, CL, Stubbe, J, Nocera, DG. 2023. J Am Chem Soc 145, 5145-5154.
    doi: 10.1021/jacs.2c11483PMID:36812162
  3. 19F Electron-Nuclear Double Resonance Reveals Interaction between Redox-Active Tyrosines across the α/β Interface of E. coli Ribonucleotide Reductase. Meyer, A, Kehl, A, Cui, C, Reichardt, FAK, Hecker, F, Funk, LM, Ghosh, MK, Pan, KT, Urlaub, H, Tittmann, K et al.. 2022. J Am Chem Soc 144, 11270-11282.
    doi: 10.1021/jacs.2c02906PMID:35652913
  4. Ribonucleotide reductase, a novel drug target for gonorrhea. Narasimhan, J, Letinski, S, Jung, SP, Gerasyuto, A, Wang, J, Arnold, M, Chen, G, Hedrick, J, Dumble, M, Ravichandran, K et al.. 2022. Elife 11, .
    doi: 10.7554/eLife.67447PMID:35137690
  5. Statistical analysis of ENDOR spectra. Pokern, Y, Eltzner, B, Huckemann, SF, Beeken, C, Stubbe, J, Tkach, I, Bennati, M, Hiller, M. 2021. Proc Natl Acad Sci U S A 118, .
    doi: 10.1073/pnas.2023615118PMID:34215694
  6. Detection of Water Molecules on the Radical Transfer Pathway of Ribonucleotide Reductase by 17O Electron-Nuclear Double Resonance Spectroscopy. Hecker, F, Stubbe, J, Bennati, M. 2021. J Am Chem Soc 143, 7237-7241.
    doi: 10.1021/jacs.1c01359PMID:33957040
  7. Gated Proton Release during Radical Transfer at the Subunit Interface of Ribonucleotide Reductase. Cui, C, Greene, BL, Kang, G, Drennan, CL, Stubbe, J, Nocera, DG. 2021. J Am Chem Soc 143, 176-183.
    doi: 10.1021/jacs.0c07879PMID:33353307
  8. Conformational Motions and Water Networks at the α/β Interface in E. coli Ribonucleotide Reductase. Reinhardt, CR, Li, P, Kang, G, Stubbe, J, Drennan, CL, Hammes-Schiffer, S. 2020. J Am Chem Soc 142, 13768-13778.
    doi: 10.1021/jacs.0c04325PMID:32631052
  9. Ribonucleotide Reductases: Structure, Chemistry, and Metabolism Suggest New Therapeutic Targets. Greene, BL, Kang, G, Cui, C, Bennati, M, Nocera, DG, Drennan, CL, Stubbe, J. 2020. Annu Rev Biochem 89, 45-75.
    doi: 10.1146/annurev-biochem-013118-111843PMID:32569524
  10. PET Polymer Recycling. O'Reilly, M, Stubbe, J. 2020. Biochemistry 59, 2316-2318.
    doi: 10.1021/acs.biochem.0c00457PMID:32559062
More Publications

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Photo Credit: Justin Knight