The Gordon Hammes Lectureship Award recognizes and honors an individual whose scientific contributions have had a major impact on research across all of biological chemistry. The winner of this year’s award, Professor JoAnne Stubbe, Professor Emerita/Novartis Professor of Chemistry/Professor of Biology, Massachusetts Institute of Technology, will present the Gordon Hammes Lecture during the ACS Fall […]
The Gordon Hammes Lectureship Award recognizes and honors an individual whose scientific contributions have had a major impact on research across all of biological chemistry. The winner of this year’s award, Professor JoAnne Stubbe, Professor Emerita/Novartis Professor of Chemistry/Professor of Biology, Massachusetts Institute of Technology, will present the Gordon Hammes Lecture during the ACS Fall 2020 Virtual Meeting & Exposition. Access the on-demand presentation here.
Since 2017, this award has been announced alongside the Gordon Hammes Scholar Award. Both awards are sponsored jointly by Biochemistry and the ACS Division of Biological Chemistry.
Professor JoAnne Stubbe
From single-electron chemistry through coordinated movements of domains, Professor Stubbe has established new paradigms and given us a legacy of brilliant discoveries. The focus of Professor Stubbe’s work has been advancing knowledge of ribonucleotide reductases, enzymes that play a crucial role in DNA replication and repair through catalyzing the conversion of nucleotides to deoxynucleotides.
The Stubbe lab undertook a range of projects focused on advancing knowledge in the area of ribonucleotide reductases including the radical propagation pathway used by Class I RNRs, interactions between protein subunits of Class I RNR, regulation of RNRs, and elucidation of the mechanisms behind the function of clinical drugs. Additional areas of research include the examination of essential metallo-cofactors of RNRs in E. coli, S. cerevisiae, and humans including their biosynthesis, activation, and regulation of their formation.
Read a brief interview with Gordon Hammes Lectureship Award Winner, Professor JoAnne Stubbe
How/why did you choose to pursue this field of research?
Since reading a paper by Tipper and Strominger in 1965 (PNAS) when I was in graduate school and taking a course in enzymology taught by Koshland and Kirsch in Biochemistry, I became interested in “rational” drug design. While I did not realize it at the time, I was interested in using my understanding of mechanism and catalysis to design specific inhibitors of therapeutic targets.
What are you working on now?
I have been retired for almost four years. In the past few years in collaboration with the Drennan lab and Nocera lab, I have continued to focus on understanding the ribonucleotide reductase enzymes (RNRs). These enzymes convert RNA building blocks to DNA building blocks in all organisms. They are sophisticated regulatory machines as they are central in controlling the relative ratios and amounts of DNA building blocks required for the fidelity of DNA replication and repair. Recently taking advantage of our ability to site-specifically incorporate unnatural amino acids into RNRs, we have made constructs of the E. coli enzyme that have allowed us to trap an “active” form of RNR with both subunits present. Kang in the Drennan was able to obtain the first structure by cryo-EM of this enzyme. Only 20 amino acids were missing from the structures of the individual subunits which we have had from structures from the Eklund lab for decades. The observation of their location for me, explained without much effort, 25 years of studies from our lab and others. Very exciting! The structure sets the stage to design new experiments to study the 32 angstrom long-range, reversible radical transfer, central for the activity of the class I RNRs. This long-range oxidation involves multiple mechanisms of proton-coupled electron transfer which the Nocera and Bennati labs have been studying in collaboration with my lab for 25 years. Exciting times for RNR discovery are ahead.
What do you anticipate working on in the future or what do you envision as future directions for the field in biochemistry?
I am writing a review article with all my collaborators to summarize what we understand about this system in general and define what we believe are the exciting and important issues that remain unresolved.
The future of biochemistry is exciting as new technologies rapidly allow experiments never dreamed of to be possible (the CRISPR revolution, Cryo-EM analysis methods to “look at” dynamic proteins such as RNR, spectroscopic and computational methods that allow us to define structures of intermediates if they can be trapped, understanding regulation inside the cell of these complex regulatory machines).
What is important in training the next generation of researchers?
The next generation, as the earlier generations, need to learn to think critically and quantitatively. They also need to be trained in some fundamental areas so that they bring something to the table. All problems are now being solved by teams of workers and productive communication of individuals with different training is essential. The rate at which discoveries are made by collaborative approaches makes science so much FUN.
What advice do you have for the next generation of researchers?
When I was a graduate student in the late 60s, there was NO molecular biology, NO internet, almost no enzyme catalysts thought to use radical based reactions, NO women role models. Times have changed and I am confident you will be able to do experiments I never dreamed of. Focus on the positive to get through the many failures that always accompany experimentation. HAVE FUN.
Explore research articles from Professor JoAnne Stubbe
Discovery of a New Class I Ribonucleotide Reductase with an Essential DOPA Radical and NO Metal as an Initiator of Long-Range Radical Transfer
Biochemistry 2019, 58, 6, 435–437
DOI: 10.1021/acs.biochem.8b01238
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PET Polymer Recycling
Biochemistry 2020, 59, 25, 2316–2318
DOI: 10.1021/acs.biochem.0c0045
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Subunit Interaction Dynamics of Class Ia Ribonucleotide Reductases: In Search of a Robust Assay
Biochemistry 2020, 59, 14, 1442–1453
DOI: 10.1021/acs.biochem.0c00001
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Properties of Site-Specifically Incorporated 3-Aminotyrosine in Proteins To Study Redox-Active Tyrosines: Escherichia coli Ribonucleotide Reductase as a Paradigm
Biochemistry 2020, 59, 14, 1442–1453
10.1021/acs.biochem.8b00160
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Photochemical Rescue of a Conformationally Inactivated Ribonucleotide Reductase
J. Am. Chem. Soc. 2018, 140, 46, 15744–15752
DOI: 10.1021/jacs.8b07902
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Conformationally Dynamic Radical Transfer within Ribonucleotide Reductase
J. Am. Chem. Soc. 2018, 140, 46, 15744–15752
DOI: 10.1021/jacs.7b08192
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The road less traveled: For love of detection, discovery, and all things radical in nature
C&EN, 2020, 98 (11), pp 37–41, March 23, 2020
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