Judith N. Burstyn

Professor of Chemistry and Pharmacology, Born 1959
B.A. 1980, Cornell University
Ph.D. 1986, University of California, Los Angeles

 

Room: 5327
Phone: 608-262-0328
Email: burstyn@chem.wisc.edu
Position: Professor

Research Description

Research Interests: Bioinorganic Chemistry, Allostery in Gas Sensing Metalloproteins, Metallosensor design

Our group studies gas-sensing metalloproteins, specifically how the interaction of a gas molecule with a metal center alters protein structure and function. Metalloproteins serve as sensors and signal transducers in a number of important biological processes. For example, NO regulates your blood pressure by interacting with heme containing soluble guanylyl cyclase. Bacteria use metalloproteins to sense gases such as O₂, CO, and NO in their environment, and plants use copper to detect ethylene, a hormone that regulates plant development.

In our laboratory, research efforts are directed towards understanding how gas sensing occurs at a metal center, and how changes in the coordination chemistry at the metal center are coupled to allosteric conformational changes in the protein. Through our studies of the mammalian NO-sensor soluble guanylyl cyclase and the bacterial CO-sensor CooA, we learned that interaction of gas molecules with the heme centers induces changes in the coordination geometry, and these changes correlate with functional changes in the proteins. Our current work aims to elucidate the mechanisms by which the coordination changes are communicated through the protein, resulting in global structural changes. To this end we study several bacterial gas-responsive transcription factors and newly discovered types of heme-containing gas sensor that regualte circadian rhythm in higher organisms.

Another project investigates the role of heme in the enzyme cystathionine-b-synthase (CBS). CBS is a critical enzyme that regulates sulfur amino acid metabolism, and this protein is the site of disease-causing mutations. We study the effect of these mutations on the biochemistry of the enzyme as a tool to understand how this unusual enzyme uses its heme.

In our studies we utilize a variety of biochemical and biophysical methods, including enzyme kinetics, protein modification or mutagenesis, mass spectrometry, electronic absorption, EPR, resonance Raman, CD and fluorescence spectroscopies, to probe the structure-function relationships. Our group is interactive and interdisciplinary, with active collaborations at UW and other institutions.

Publications

• “Ferric, Not Ferrous, Heme Activates DGCR8 for Primary microRNA Processing” Ian Barr, Aaron T. Smith, Yanqiu Chen, Rachel Senturia, Judith N. Burstyn, Feng Guo, Proc. Natl. Acad. Sci. 2012, 109, 1919-1924.

• “Cobalt Cystathionine β-Synthase: A Cobalt-Substituted Heme Protein With a Unique Thiolate Ligation Motif” Aaron T. Smith, Tomas Majtan, Katherine M. Freeman, Judith N. Burstyn, Jan P. Kraus Inorganic Chemistry, 2011, 50, 4417–4427.

• “Purification and characterization of cystathionine beta-synthase bearing a cobalt protoporphyrin” Tomas Majtan, Katherine M. Freeman, Aaron T. Smith, Frank E. Frerman, Judith N. Burstyn, Jan P. Kraus Arch. Biochem. Biophys. 2011, 508, 25–30.

• “DiGeorge Critical Region 8 (DGCR8) Is a Double-Cysteine-Ligated Heme Protein” Ian Barr, Aaron T. Smith, Rachel Senturia, Yanqiu Chen, Brooke D. Scheidemantle, Judith N. Burstyn, Feng Guo J. Biol. Chem. 2011, 286, 16716-16725.

• “Nitric Oxide Photogeneration from trans-Cr(cyclam)(ONO)₂⁺ in a Reducing Environment. Activation of Soluble Guanylyl Cyclase and Arterial Vasorelaxation” Alexis D. Ostrowski, Sherine J. Deakin, Bilal Azhar, Thomas W. Miller, Nestor Francoleon, Melisa M. Cherney, Andrea Lee, Judith N. Burstyn, Jon M. Fukuto, Ian L. Megson, Peter C. Ford, J. Med. Chem. 2010, 53, 715–722 715; DOI: 10.1021/jm9013357.

• “The effects of nitroxyl (HNO) on soluble guanylyl cyclase activity: Interactions at ferrous heme and cysteine thiols“ Thomas W. Miller, Melisa M. Cherney, Andrea J. Lee, Nestor E. Francoleon, Patrick J. Farmer, S. Bruce King, Adrian J. Hobbs, Katrina M. Miranda, Judith N. Burstyn, Jon M. Fukuto, Journal of Biological Chemistry, 2009, 284, 21788-21796. DOI: 10.1074/jbc.M109.014282. 

• “Nuclear receptors Homo sapiens Rev-erbβ and Drosophila melanogaster E75 are thiolate-ligated heme proteins, which undergo redox-mediated ligand switching and bind CO and NO” Katherine A. Marvin, Jeffrey L. Reinking, Andrea J. Lee, Keith Pardee, Henry M. Krause, Judith N. Burstyn, Biochemistry, 2009, 48, 7056–7071. DOI: 10.1021/bi900697c. 

• “Photophysical Characteristics and Reactivity of Bis(2,9-di-tert-butyl-1,10-phenanthroline)Cu(I)” Omar Green, Bhavesh A. Gandhi, Judith N. Burstyn, Inorganic Chemistry, 2009, 48, 5704–5714. DOI: 10.1021/ic802361q. 

• “Guanidine Hydrochloride-Induced Unfolding of the Three Heme Coordination States of the CO-Sensing Transcription Factor, CooA” Andrea J. Lee, Robert W. Clark, Hwan Youn, Sarah Ponter, Judith N. Burstyn, Biochemistry, 2009, 48, 6585-6597. DOI: 10.1021/bi801827j. 

• "The CO-activated transcription regulator RcoM-2 from Burkholderia xenovorans is a cysteine-ligated hemoprotein that undergoes a redox-mediated ligand switch" Katherine A. Marvin, Robert L. Kerby, Hwan Youn, Gary P. Roberts, Judith N. Burstyn, Biochemistry, 2008, 47, 9016-9028.

Awards

• Fellow of the American Association for the Advancement of Science 2009

• Vilas Associates Award (2005-2006)

• Doris Slesinger Award for Excellence in Mentoring (2005)

• Fellow of UW-Madison Teaching Academy (2004)

• Women in Engineering Program Award (Women in Science and Engineering Residential Program, UW-Madison; Co-Directors Judith N. Burstyn and Wendy C. Crone)

• Alfred P. Sloan Research Fellow  (1996-1998)

• Dave McClain Research Award, American Heart Association, Wisconsin Affiliate  (1994)
  

• Alumni Distinguished Service Award, University of Wisconsin-Eau Claire  (1987)

• Aid for Cancer Research Fellow  (1987-1989 -declined)

• American Cancer Society Postdoctoral Fellow  (1987-1989)