Pablo Sobrado


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

B.A., Biology, Merrimack College, MA 1993


  • May 2012 – present: Associate Professor Department of Biochemistry, Virginia Tech, Blacksburg, VA
  • January 2012 – present: Director, Virginia Tech Center for Drug Discovery Screening Laboratory, Virginia Tech, Blacksburg, VA
  • August 2007 – May 2012: Assistant Professor, Department of Biochemistry, Virginia Tech, Blacksburg, VA
  • August 2004 – July 2007: Research Associate, Department of Biochemistry, University of Wisconsin, Madison, WI- With Dr. Brian Fox
  • August 2003 – July 2004: Postdoctoral Fellow, Department of Molecular Biosciences, University of Chile, Santiago, Chile- With Prof. Jorge Allende.

Selected Major Awards

  • 2013 – Everson Lecture  University of Wisconsin, Madison, WI
  • 2011 –National Technology Prize, Chlodomido Picado Twight, Costa Rica
  • 2011 –Grand Marshal, Central America Independence Day Celebration, Los Angeles, CA
  • 2011 –Founding Member of Virginia Tech’s Center for Drug Discovery, Development (VTCDD)
  • 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 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 scientist.

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).
  • Han, A., Robinson, R., Badieyan, S., Ellerbrock, J. Sobrado, P. (2013) Tryptophan-47 in the active site of Methylophaga sp. Strain SK1 flavin monooxygenase is important for hydride tranfer. Arch. Biochem. Biophys. 532. 46-53.
  • Kizjakina, K., Tanner, J.J., Sobrado, P. (2013). Targeting UDP-galactopyranose Mutases from Eukaryotic Human Pathogen. Current Pharmaceutical Design. 19. 2561-73.
  • Dhatwalia, R., Singh, H.,  Solano, L.M., Oppenheimer, M., Robinson, R.,  Ellerbrock, J.E.,  Sobrado, P., Tanner, J.J. (2012) Identification of the NAD(P)H Binding Site of Eukaryotic UDP-Galactopyranose Mutase. J. Am. Chem. Soc. 134. 18132-8 (recommended by Faculty of 1000)
  • Sobrado, P., Noncanonical reactions of flavoenzymes. (2012) Int. J. Mol. Sci. 13. 14219-14242.
  • Franceschini S, Fedkenheuer M, Vogelaar NJ, Robinson HH, Sobrado P, Mattevi A. (2012) Structural insight into the mechanism of oxygen activation and substrate selectivity of flavin-dependent N-hydroxylating monooxygenases. Biochemistry. 51.7043-5.
  • Dhatwalia, R., Singh, H., Oppenheimer, M., Sobrado, P., Tanner, J.J. (2012) Crystal Structures of Trypanosoma cruzi UDP-Galactopyranose Mutase Implicate Flexibility of the Histidine Loop in Enzyme Activation. Biochemistry. 51. 4968-79.
  • Romero, E., Fedkenheuer, M., Chocklett, S.W., Qi, J., Oppenheimer, M., Sobrado, P., (2012). Dual role of NADP(H) in the reaction of a flavin dependent N-hydroxylating monooxygenase. Biochim. Biophys. Acta. 6. 850-7.
  • Dhatwalia, R., Singh, H., Oppenheimer, M., Karr, D.B., Nix, J.C., Sobrado, P., Tanner, J.J., (2012) Crystal structures and small-angle X-ray scattering analysis of UDP-galactopyranose mutase from the pathogenic fungus Aspergillus fumigatus. J. Biol. Chem. 286. 9041-51.
  • Oppenheimer, M., Valenciano, A.L., Kizjakina, K., Qi, J. Sobrado, P., (2012) Chemical Mechanism of UDP-Galactopyranose Mutase from Trypanosoma cruzi: a Potential Drug Target Against Chagas’ Disease, PLoS ONE. 7(3) e32918.
  • Romero, E., Robinson, R., Sobrado, P., (2012) Monitoring the Reductive and Oxidative Half-Reactions of a Flavin Dependent Monooxygenase Using Stopped-flow Spectrophotometer. JoVe. 61.
  • Qi, J., Robinson, R., Sobrado, P. (2012) A Fluorescence Polarization Binding Assay to Identify Inhibitors of Flavin-Dependent Monooxygenases. Analytical Biochemistry. 425. 80-7. 
  • Tanner, J., Boechi, L., McCammon, J.A., Sobrado, P. (2014) Structure, Mechanism, and Dynamics of UDP-Galactopyranose Mutase. Arch. Biochem. Biophys. 544. 128-141. Review. Selected for the Cover
  • Robinson, R., Franceschini, S., Fedkenheuer, M., Rodriguez, P., Ellerbrock, P., Romero, E., Echandi, M.P., Martin del Campo, J., Sobrado, P. (2014) Arg279 is the key regulator of coenzyme selectivity in the flavin-dependent ornithine monooxygenase SidA. Biochim. Biophys. Acta. 1844. 778-784.
  • Robinson, R., Rodriguez, P., Sobrado, P. (2014) Mechanistics studies on the flavin-dependent N6-lysine monooxygenase MbsG reveal an unusual control for catalysis. Arch. Biochem. Biophys. 550-551, 58-66.
  • Da Fonseca, I., Qureshi, I.A., Mehra-Chaudharay, R., Kizjakina, K., Tanner, J.J., Sobrado, P.  (2014) Contributions of Unique Active Site Residues of Eukaryotic UDP-Galactopyranose Mutases to Substrate Recognition and Active Site Dynamics. Biochemistry. 53, 7794-7804.