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Eric Strieter

Website | Awards | Publications

Assistant Professor

B.S. 1999, University of Wisconsin-Madison

Ph.D. 2005, Massachusetts Institute of Technology

American Cancer Society Postdoctoral Fellow, 2009, Harvard Medical School

Room: 5112a
Phone: 608-265-8431
Email: strieter@chem.wisc.edu
Position: Assistant Professor

Selected Publications

  • "Cascade reactions during coronafacic acid biosynthesis: elongation, cyclization, and functionalization during Cfa7-catalyzed condensation."  Strieter, E. R.; Koglin, A.; Aron, Z. D.; Walsh, C. T. J. Am. Chem. Soc. 2009, 131, 2113

  • "Mechanistic studies on the copper-catalyzed N-arylation of amides." Strieter, E. R.; Bhayana, B.; Buchwald, S. L. J. Am. Chem. Soc. 2009, 131, 78.

  • "Structural basis for the selectivity of the external thioesterase of the surfactin synthetase." Koglin, A.; Löhr, F.; Bernhard, F.; Rogov, V. R.; Frueh, D. P.; Strieter, E. R.; Mofid, M. R.; Güntert, P.; Wagner, G.; Walsh, C. T.; Marahiel, M. A.; Dötsch, V. Nature, 2008, 454, 907.

  • "Water-mediated catalyst preactivation: an efficient protocol for C-N cross-coupling reactions." Fors, B. P.; Krattiger, P.; Strieter, E. R.; Buchwald, S. L. Org. Lett. 2008, 10, 3505.

  • "CmaE: A Transferase Shuttling Aminoacyl Groups between Carrier Protein Domains in the Coronamic Acid Biosynthetic Pathway." Strieter, E. R.; Vaillancourt, F. H.; Walsh, C. T. Biochemistry 2007, 46, 7549.

  • "Reevaluation of the Mechanism of the Amination of Aryl Halides Catalyzed by BINAP-Ligated Palladium Complexes." Shekhar, S.; Ryberg, P.; Hartwig, J. F.; Mathew, J. S.; Blackmond, D. G.; Strieter, E. R.; Buchwald, S. L. J. Am. Chem. Soc. 2006, 128, 3584.

  • "Evidence for the Formation and Structure of Palladacycles During the Pd-Catalyzed C-N Bond-Forming Reaction with Catalysts Derived From Bulky Monophosphinobiaryl Ligands." Strieter, E. R.; Buchwald, S. L. Angew. Chem. Int. Ed. 2006, 45, 925.

  • "New Insights into Xantphos/Pd-Catalyzed C-N Bond-Forming Reactions: A Structural and Kinetic Study."  Klingensmith, L. M.; Strieter, E. R.; Barder, T. E.; Buchwald, S. L. Organometallics 2006, 25, 82.

  • "The Role of Chelating Diamine Ligands in the Goldberg Reaction: A Kinetic Study on the Cu-Catalyzed Amidation of Aryl Iodides." Strieter, E. R.; Blackmond, D. G.; Buchwald, S. L. J. Am. Chem. Soc. 2005, 127, 4120.

  • "Insights into the Origin of High Activity and Stability of Catalysts Derived from Bulky, Electron-Rich Monophosphinobiaryl Ligands in the Pd-Catalyzed C-N Bond Formation." Strieter, E. R.; Blackmond, D. G.; Buchwald, S. L. J. Am. Chem. Soc. 2003,125, 13978.

Research Description


Chemistry and Biology of Protein

Ubiquitination and Degradation

The entire population of proteins in an organism, known as the proteome, is dynamic and rich in diversity. It is estimated that the human proteome consists of >200,000-2,000,000 distinct protein forms despite only 20,000 proteins encoded by the genome. Giving rise to this complexity are the myriad covalent modifications that occur on the side chains of amino acid residues embedded within proteins. The ensemble of alterations is termed posttranslational modifications (PTMs), reflecting the timing within the context of the central dogma in biology. PTMs consist of the covalent attachment of both small molecules (phosphate, methyl, glycosyl, or acetyl) and proteins, e.g., ubiquitin and ubiquitin-like molecules (UBLs). Many PTMs are entwined with one another resulting in dramatic physiological changes if a single node within the cellular network is malfunctioning. Take for example, the two most abundant mechanisms for regulating protein function, phosphorylation and ubiquitination. Their codependence during the cell cycle and immune response relates miscues to aberrant cellular events on a global scale ultimately leading to the development of immune disorders and cancer. Against this backdrop, our laboratory is interested in the molecular details associated with the tethering of ubiquitin and UBLs to proteins. An intricate network of enzymes are responsible for carrying out the coupling and uncoupling of ubiquitin/UBLs to and from target proteins. Specifically, three types of enzyme — E1, E2, and E3 — attach ubiquitin/UBLs, and in most cases, assemble polymeric chains of ubiquitin molecules tethered to substrates. E1s activate ubiqutin/UBLs. E2s transfer ubiquitin/UBLs from E1 and couple them to an ε-amino group of a lysine residue in the target, while E3s sequester specific substrates catalyzing the ligation to targets. The outcome of these steps can be reversed through the action of deubiquitylating enzymes (DUBs). Although a great deal is known about the overall ubiquitin cascade, it is unclear how the communication between E2-E3 controls ubiquitination; which substrates a given E3 is responsible for modifying; and how E3-catalyzed polyubiquitin chain formation occurs on a molecular level. Answers to these questions are not only critical for the development of new therapeutics but also for the functional interpretation of mutant forms of enzymes that lead to human disease. To address these questions we use ideas and methods from organic chemistry, biochemistry, molecular biology and cell biology.

 



 

 


 

 

Awards

  • Shaw Scientist - 2010

  • American Cancer Society Post-doctoral Fellowship, 2005-2008

  • ACS Division of Organic Chemistry Graduate Fellowship, 2003-2004

  • UW-Madison Hilldale Fellowship for Undergraduate Research, 1999