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Pablo Sobrado

  • Research area(s): Mechanisms and Regulation of Enzymes


Ph.D., Biochemistry and Biophysics, Texas A&M University, Texas, 2003

B.A., Biology, Merrimack College, Massachusetts, 1997


  • 2019 - Associate Department Head, Department of Biochemistry, Virginia Tech, Blacksburg, VA
  • 2019 - Associate Director, Virginia Tech Center for Drug Discovery, Virginia Tech, Blacksburg, VA
  • 2016 - Professor, Department of Biochemistry, Virginia Tech, Blacksburg, VA
  • 2015 - Graduate Program Director, Department of Biochemistry, Virginia Tech, Blacksburg, VA
  • 2016 - Professor of Health Sciences, Virginia Tech, Blacksburg, VA
  • 2012 - Director,  Virginia Tech Drug Screening Laboratory, Virginia Tech, Blacksburg, VA
  • 2010 - Adjunct Professor, Department of Biology, Costa Rica Institute of Technology, Cartago, Costa Rica
  • 2012 - 2016 - Associate Professor, Department of Biochemistry, Virginia Tech, Blacksburg, VA
  • 2014 - 2016 - Associate Professor of Health Sciences, Virginia Tech, Blacksburg, VA
  • 2007 - 2012 - Assistant Professor, Department of Biochemistry, Virginia Tech, Blacksburg, VA
  • 2004 - 2007 - Research Associate, Department of Biochemistry, University of Wisconsin, Madison, WI Advisor: Dr. Brian G. Fox
  • 2003 - 2004 - Postdoctoral Fellow, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile, Advisor: Dr. Jorge E. Allende


  • 2017 - Keynote Speaker, 8th Southeast Enzyme Conference, Atlanta, GA
  • 2014 - Excellence in Basic Research Award from the College of Agriculture and Life Sciences
  • 2014 - ASBMB Research Spotlight for the month of March
  • 2013 - Everson Lecture, University of Wisconsin, Madison, WI
  • 2011 - National Technology Prize, Clodomiro Picado Twight, Costa Rica
  • 2011 - Grand Marshal, Central America Independence Day Celebration, Los Angeles, CA
  • 2010 - J. Shelton Horsley Research Award from the Virginia Academy of Sciences
  • 2009 - Allan T. Gwathmey Chemistry Award from the Virginia Academy of Sciences
  • 2009 - Ralph Powe Junior Faculty Enhancement Award from the Oak Ridge Associated Universities (ORAU)
  • 2005-07 - American Heart Association Postdoctoral Fellowship

Courses Taught

BCHM 2114: Biochemical Calculations

BCHM 5004: Biochemistry Seminar

BCHM 5242: Protein Structure and Function

BCHM 4224: Biochemistry Laboratory

Other Teaching and Advising 

  • Mentor undergraduate (> 30) students on their independent research projects.
  • I also advise undergraduate Biochemistry students.
  • I mentor several graduate and postdoctoral scientists.

Program Focus

My primary research focus is on the study of the mechanisms of action, regulation, and structure of enzymes. Knowledge of enzyme structure and function is essential to our understanding of the origins of genetic and degenerative diseases and for providing clues for the identification of drugs against infectious diseases, cancers, or metabolic disorders. As model systems, I have chosen to study enzymes that catalyze two different chemical reactions: 1) sugar ring contraction, and 2) hydroxylation. Specifically, we study enzymes that 1) are essential for bacterial development, and 2) are important for fungal or parasitic pathogenesis. By selecting enzymes that are important for the growth of microbial pathogens, apart from increasing our understanding of how enzymes function, our research will lead to the development of novel chemotherapeutic agents against several human diseases.

Current Projects

  1. Sugar ring contraction: UDP-Galactopyranose mutase. Galactofuranose (Galf) is a sugar molecule that is present in many human pathogens as an essential component of the bacterial cell wall. Galf has been shown to be important in the mechanism of infection of the parasites Trypanosoma cruzi and Leishmania major and in the fungus Aspergillus fumigatus. These human pathogens are the causative agents of Chagas’ disease, leishmaniasis, and aspergillosis, respectively. Combined, these microbes infect close to 1 million people and are responsible for more than 100,000 deaths per year. There are no effective drugs for the treatment of any of these diseases. Since Galf is involved in pathogenesis, inhibiting the production of this sugar might prevent infections by these microbes.

    We have chosen to study the enzyme UDP-galactopyranose mutase (UGM), which is responsible for the conversion of UDP-galactopyranose to UDP-galactofuranose, the rate-determining step in the biosynthesis of Galf. This enzyme is not present in humans, thus, drugs that are able to inhibit it should not cross-react with native human enzymes. We are studying the mechanism of action and determining the structure of UGM to gain information regarding the structure of the active site, transition state intermediates, and essential functional groups. We are working with Dr. Jack Tanner at the University of Missouri, Columbia, to obtain the structures of these enzymes. This information will be used to design inhibitors against UGM that can block the biosynthesis of Galf in vivo, thus, preventing microbial growth or infection. These compounds may lead to the development of novel drugs for the treatment of Chagas’ disease, leishmaniasis, and aspergillosis. This project is supported by NIH grant RO1 GM094469.
  2. Hydroxylation: Flavin-dependent Siderophore Hydroxylases. Iron is an essential nutrient for bacterial and fungal growth but is unavailable to invading microbial pathogens in humans as it is sequestered by iron binding proteins such as transferrin, lactoferrin, and hemoglobin. To overcome this iron deficiency, pathogenic microbes synthesize and secrete low-molecular-weight iron chelators, called siderophores, to scavenge iron from the host. Siderophores are synthesized via non-ribosomal peptide synthetases containing functional groups such as carboxylates, catecholates, and hydroxamates, which are essential for binding the metal iron. Hydroxamate functional groups are commonly derived from the hydroxylation of the terminal amino group of the amino acids L-lysine or L-ornithine. This reaction is catalyzed by flavin-dependent monooxygenases. Deletion of MbtG, the flavoprotein that catalyzes the hydroxylation of lysines present in mycobactin, the siderophore of Mycobacterium tuberculosis, has been shown to be essential for mycobacterial survival. Similarly, in Aspergillus fumigatus, the N5-ornithine hydroxylase (SidA) has been shown to be essential for pathogenesis and survival in this fungus. We have chosen to study these enzymes because there is no information about their structure or mechanism of action. In addition, these enzymes represent ideal drug targets because they are not found in humans. I have established an international collaboration with Dr. Andrea Mattevi (University of Pavia, Italy), who is a leader in the field of structural biology of flavin-dependent enzymes, to determine the three-dimensional structure of MbtG and SidA. Our work will allow us to establish if there are differences in the structure and function between the eukaryotic (Aspergillus) and prokaryotic (Mycobacterium) enzymes. Furthermore, we will learn the mechanism of substrate selectivity that allows for hydroxylation of ornithine versus lysine. This work is supported in part by grant from the National Science Foundation (MCB 1021384).

Cossio-Pérez R, Pierdominici-Sottile G, Sobrado P, and Palma J. Molecular Dynamics Simulations of Substrate Release from Trypanosoma cruzi UDP-Galactopyranose Mutase. J Chem Inf Model. 2019 Feb 25;59(2):809-817.

Valentino H, and Sobrado P. (2019) Performing anaerobic stopped-flow spectrosphotometry inside of an anaerobic chamber. Methods Enzymol. 2019;620:51-88.

Robinson, R., Klancher, C., Rodriguez, P., and Sobrado, P. (2018) Flavin oxidation in flavin dependent N-monooxygenase. Protein Science, 1:90-99.

Dai, Y., Valentino, H., and Sobrado, P. (2018) Evidence for Formation of a Radical-Mediated Flavin-N5 Covalent Intermediate. ChemBioChem. 54:3713-3721

Pierdominicci-Sotteli, G., Cossio-Perez, R., Da Fonseca, L, Kizjakina, K., Tanner, J.J., and Sobrado, P. (2018) Steric Control of the Rate Limiting-Step of UDP-Galactopyranose Mutase. Biochemistry. 57:3713-3721

Gadda, G., and Sobrado, P. (2018) Kinetic Solvent Viscosity Effects as Probes to Study the Mechanisms Enzyme Action. Biochemistry. Biochemistry. 57:3445-34453.

Li-Kai, L., Dai, Y., Abdelwahad, H., and Sobrado, P., Tanner, J.J. (2018) Structural evidence for rifampicin monooxygenase inactivating rifampicin by cleaving its ansa-bridge. Biochemistry. 57:2065-68.

Dai, Y., Kizjakina, K., Campbell, A.C., Korasick. D.A., Tanner, J.J, and Sobrado, P. (2018) Flavin-N5 Covalent Intermediate in the Non-redox Dehalogenation Reaction Catalyzed by an Atypical Flavoenzyme. ChemBioChem. 19:53-57.

Bufkin, K., and Sobrado, P. (2017) Characterization of the Ornithine Hydroxylation Step in Albachelin Biosynthesis. Molecules 22:1652.

Sobrado, P., and Gadda, G. (2017) Introduction to flavoproteins: Beyond the classical paradigms. Arch. Biochem. Biophys. 632:1-3

Martin Del Campo, J.S., M. Eckshtain-Levi, and Sobrado, P. (2017) Identification of eukaryotics UDP-galactopyranose mutase inhibitors using the ThermoFAD assay. Biochem. Biopys. Res. Cummun. 493:58-63.

Martin Del Campo, J.S., M. Eckshtain-Levi, N. Vogelaar, and  Sobrado, P (2017) Identification of Aspergillus fumigatus UDP-galactopyranose mutase inhibitors. Sci Rep. 7:10836.

Webb, B., Compton, K.,  Martin Del Campo, J.S., Taylor, D., and Sobrado, P., Scharf, B.E. (2017) Sinorhizobium meliloti chemotaxis to multiple amino acids is mediated by chemoreceptor McpU.  Mol. Plat. Microbe. Interact. 10: 770-777.

Sobrado, P., and Tanner, J.J. (2017) Multiple functionalities of reduced flavin in the non-redox reaction catalyzed by UDP-galactopyranose mutase. Arch. Biochem. Biophys. 632:59-65.

Sobrado, P., Gadda, G., Introduction to flavoproteins: Beyond the classical paradigms.(2017)  Arch. Biochm. Biophys. 632:1-3.