Faculty Guide

Title

Professor of Biology

Biology
Health: Science, Society, and Policy

Expertise

Enzyme mechanisms and structure-function relationships. Design and evaluation of enzyme inhibitors.

Awards and Honors

American Association for the Advancement of Science Fellow (2010)

Louis D. Brandeis Teaching Award (2007)

Faculty Early Career Development Award, Directorate for Biological Sciences, National Science Foundation (1995 - 1999)

Young Investigator Award, Arnold and Mabel Becknman Foundation (1995 - 1997)

Searle Scholar (1993 - 1996)

Courses Taught

BCHM	101a	Advanced Biochemistry: Enzyme Mechanisms
BCHM	103b	Advanced Biochemistry: Information Transfer Mechanisms
BISC	8b	Drugs that Changed the World
CBIO	106b	Chemical Biology: Medicinal Enzymology

Scholarship

Pan, Yue; Long, Marcus J. C.; Lin, Hsin-Chieh; Hedstrom, Lizbeth and Xu, Bing. "Magnetic Nanoparticles for Direct Protein Sorting inside Live Cells." Chemical Science (2013). (forthcoming)

Gao, Yua, Long, Marcus J.C; Shi, Junfeng; Hedstrom, Lizbeth and Xu, Bing. "Using supramolecular hydrogel to discover the interactions between proteins and molecular nanofibers of small molecules." Chem. Commun. (Camb) 48. (2013): 8404-6.

Hedstrom, Lizbeth. "IMP dehydrogenase: the dynamics of reaction specificity." Proceedings of the 5th International Beilstein Symposium on Experimental Standard Conditions of Enzyme Characterizations (ESCEC)., 2013

Johnson, Corey R.; Gorla, Suresh Kumar; Kavitha, Mandapati; Zhang, Minjia; Liu, Xiaoping; Striepen, Boris; Mead, Jan R.; Cuny, Gregory D. and Hedstrom, Lizbeth. "Phthalazinone Inhibitors of Inosine-5’-Monophosphate Dehydrogenase from Cryptosporidium parvum." Biorg. Med. Chem. Lett. 23. (2013): 1004-7.

Gorla, Suresh Kumar; Kavitha, Mandapati; Zhang, Minjia; Liu, Xiaoping; Sharling, Lisa; Gollapalli, Deviprasad R; Striepen, Boris; Hedstrom, Lizbeth and Cuny, Gregory D.. "Selective and potent urea inhibitors of Cryptosporidium parvum inosine 5’-monophosphate dehydrogenase." J. Med. Chem. 55. 7759-71 (2012).

Hansen, B. G., Sun, X. E., Genee, H. J., Kaas, C. S., Nielsen, J. B., Mortensen, U. H., Frisvad, J. C., Hedstrom, L.. "Adaptive evolution of drug targets in producer and non-producer organisms." Biochemical Journal 441. (2012): 219-226.

Hedstrom, Lizbeth. "The dynamic determinants of reaction specificity in the IMPDH/GMPR family of (β/α)8 barrel enzymes." Critical Reviews In Biochemistry & Molecular Biology 47. (2012): 250-63.

Kirubakaran, S., Gorla, S. K., Sharling, L., Zhang, M. J., Liu, X. P., Ray, S. S., MacPherson, I. S., Striepen, B., Hedstrom, L., Cuny, G. D.. "Structure-activity relationship study of selective benzimidazole-based inhibitors of Cryptosporidium parvum IMPDH." Bioorganic & Medicinal Chemistry Letters 22. 5 (2012): 1985-1988.

Long, Marcus J. C. and Hedstrom, Lizbeth. "Mushroom Tyrosinase Oxidizes Tyrosine-rich Sequences, Allowing Selective Protein Functionalization." ChemBiochem 13. (2012): 1818-25.

Long, Marcus J. C., Gollapalli, Deviprasad R. and Hedstrom, Lizbeth. Inhibitor Mediated Protein Degradation. Chemistry & Biology 19, 629-37 (2012). Nature News & Views. "Inhibitor Mediated Protein Degradation." Chemistry & Biology 19. (2012): 629-37.

Makowska-Grzyska, M.; Kim, Y.; W., R.; Wilton, R.; Gollapalli, D.R.; *Wang, X.K.; Zhang, R.; Jedrzejczak, R.; Mack, J.C.; Maltseva, N.; Mulligan, R.; Binkowski, T.A; Gornicki, P.; Kuhn, M.; Anderson, W.F.; Hedstrom, L and Joachimiak, A.. "Bacillus anthracis IMP Dehydrogenase in Action: Structures of Apoenzyme and in Complex with Substrate and Product." Biochemistry 51. (2012): 6148-6163.

McGrew, D. A., Hedstrom, L.. "Towards a Pathological Mechanism for IMPDH1-Linked Retinitis Pigmentosa." Retinal Degenerative Diseases 723. (2012): 539-545.

Gorla, Suresh Kumar; Johnson, Corey; Khan, Jihan; Sun, Xin; Sharling, Lisa; Striepen, Boris and Hedstrom, Lizbeth.. "Targeting prokaryotic enzymes in the eukaryotic pathogen Cryptosporidium." Apicomplexan Parasites: Molecular Approaches toward Targeted Drug Development. vol. 2 Ed. book editor: Katja Becker; series editor:. Wiley-Blackwell, 2011. 271-286.

Hedstrom, Lizbeth; Liechti, George; Goldberg, Joanna B. and Gollapalli, Deviprasad R.. "The antibiotic potential of prokaryotic IMP dehydrogenase inhibitors.." Current Medicinal Chemistry 18. (2011): 1909-18.

Hoefler, B. C., Gollapalli, D. R., Hedstrom, L.. "Specific biotinylation of IMP dehydrogenase." Bioorganic & Medicinal Chemistry Letters 21. 5 (2011): 1363-1365.

Hoefler, B. Christopher; Gollapalli, Deviprasad R. and Hedstrom, Lizbeth.. "Specific Biotinylation of IMP Dehydrogenase.." Bioorg. Med. Chem. Lett. 21. 5 (2011): 1363-1365.

Long, M. J. C., Pan, Y., Lin, H. C., Hedstrom, L., Xu, B.. "Cell Compatible Trimethoprim-Decorated Iron Oxide Nanoparticles Bind Dihydrofolate Reductase for Magnetically Modulating Focal Adhesion of Mammalian Cells." Journal of the American Chemical Society 133. 26 (2011): 10006-10009.

MacPherson, I. S., Temme, J. S., Habeshian, S., Felczak, K., Pankiewicz, K., Hedstrom, L., Krauss, I. J.. "Multivalent Glycocluster Design through Directed Evolution." Angewandte Chemie-International Edition 50. 47 (2011): 11238-11242.

Pan, Yue; Long, Marcus J. C.; Li, Xinming; Shi, Junfeng; Hedstrom, Lizbeth & Bing Xu.. "Glutathione (GSH)-decorated magnetic nanoparticles for binding glutathione-S-transferase (GST) fusion protein and manipulating live cells." Chemical Science 2. (2011): 945-8.

Patton, G. C., Stenmark, P., Gollapalli, D. R., Sevastik, R., Kursula, P., Flodin, S., Schuler, H., Swales, C. T., Eklund, H., Himo, F., Nordlund, P., Hedstrom, L.. "Cofactor mobility determines reaction outcome in the IMPDH and GMPR (beta-alpha)(8) barrel enzymes." Nature Chemical Biology 7. 12 (2011): 950-958.

Riera, T. V., Zheng, L. Q., Josephine, H. R., Min, D. H., Yang, W., Hedstrom, L.. "Allosteric Activation via Kinetic Control: Potassium Accelerates a Conformational Change in IMP Dehydrogenase." Biochemistry 50. 39 (2011): 8508-8518.

Sun, X. E., Hansen, B. G., Hedstrom, L.. "Kinetically Controlled Drug Resistance HOW PENICILLIUM BREVICOMPACTUM SURVIVES MYCOPHENOLIC ACID." Journal of Biological Chemistry 286. 47 (2011): 40595-40600.

Gollapalli, Deviprasad R.; MacPherson, Iain S.; Liechti, George; Goldberg, Joanna B. and Hedstrom, Lizbeth. "Structural Determinants of Inhibitor Selectivity in Prokaryotic IMP Dehydrogenases." Chemistry and Biology 17. 10 (2010): 1084-1091.

Josephine, Helen R.; *Ravichandran, Kanchana R. and Hedstrom, Lizbeth.. "The Cys319 loop modulates the transition between dehydrogenase and hydrolase conformations in IMP dehydrogenase." Biochemistry 49. 50 (2010): 10674-81.

Macpherson, I. S., Kirubakaran, S., Gorla, S. K., Riera, T. V., D'Aquino, J. A., Zhang, M., Cuny, G. D., Hedstrom, L.. "The structural basis of Cryptosporidium -specific IMP dehydrogenase inhibitor selectivity." J Am Chem Soc 132. 4 (2010): 1230-1.

Mansfield, Bryce E.; Oltean, Hanna N.; Oliver, Brian G.; Leyde, Sarah E.; Hedstrom, Lizbeth and White, Theodore C.. "Azole Drug Import Requires a Transporter in Candida albicans and Other Pathogenic Fung." PLoS Pathogens 6. 9 (2010): e1001126.

Sharling, Lisa: Liu, Xiaoping; Gollapalli, Deviprasad R.; Maurya, Sushil; Hedstrom, Lizbeth and Striepen, Boris.. "A screening pipeline for antiparasitic agents targeting Cryptosporidium inosine monophosphate dehydrogenase.." PLoS Neglected Tropical Diseases 4. 8 (2010): e794.

Sun, X. E., Sharling, L., Muthalagi, M., Mudeppa, D. G., Pankiewicz, K. W., Felczak, K., Rathod, P. K., Mead, J., Striepen, B., Hedstrom, L.. "Prodrug activation by Cryptosporidium thymidine kinase." J Biol Chem 285. 21 (2010): 15,916-15,922.

Hedstrom, L.. "IMP dehydrogenase: structure, mechanism, and inhibition." Chem Rev 109. 7 (2009): 2903-28.

Maurya, S. K., Gollapalli, D. R., Kirubakaran, S., Zhang, M., Johnson, C. R., Benjamin, N. N., Hedstrom, L., Cuny, G. D.. "Triazole inhibitors of Cryptosporidium parvum inosine 5'-monophosphate dehydrogenase." J Med Chem 52. 15 (2009): 4623-30.

Sazonova, I. Y., McNamee, R. A., Houng, A. K., King, S. M., Hedstrom, L., Reed, G. L.. "Reprogrammed streptokinases develop fibrin-targeting and dissolve blood clots with more potency than tissue plasminogen activator." J Thromb Haemost 7. 8 (2009): 1321-8.

Hedstrom, L.. "IMP dehydrogenase-linked retinitis pigmentosa." Nucleosides Nucleotides Nucleic Acids 27. 6 (2008): 839-49.

Min, D., Josephine, H. R., Li, H., Lakner, C., MacPherson, I. S., Naylor, G. J., Swofford, D., Hedstrom, L., Yang, W.. "An enzymatic atavist revealed in dual pathways for water activation." PLoS Biol 6. 8 (2008): e206.

Mortimer, S. E., Xu, D., McGrew, D., Hamaguchi, N., Lim, H. C., Bowne, S. J., Daiger, S. P., Hedstrom, L.. "IMP dehydrogenase type 1 associates with polyribosomes translating rhodopsin mRNA." J Biol Chem 283. 52 (2008): 36354-60.

Riera, T. V., Wang, W., Josephine, H. R., Hedstrom, L.. "A kinetic alignment of orthologous inosine-5'-monophosphate dehydrogenases." Biochemistry 47. 33 (2008): 8689-96.

Umejiego, N. N., Gollapalli, D., Sharling, L., Volftsun, A., Lu, J., Benjamin, N. N., Stroupe, A. H., Riera, T. V., Striepen, B., Hedstrom, L.. "Targeting a prokaryotic protein in a eukaryotic pathogen: identification of lead compounds against cryptosporidiosis." Chem Biol 15. 1 (2008): 70-7.

Xu, D., Cobb, G., Spellicy, C. J., Bowne, S. J., Daiger, S. P., Hedstrom, L.. "Retinal isoforms of inosine 5'-monophosphate dehydrogenase type 1 are poor nucleic acid binding proteins." Arch Biochem Biophys (2008).

Chen, L., Gao, G., Felczak, K., Bonnac, L., Patterson, S. E., Wilson, D., Bennett, E. M., Jayaram, H. N., Hedstrom, L., Pankiewicz, K. W.. "Probing binding requirements of type I and type II isoforms of inosine monophosphate dehydrogenase with adenine-modified nicotinamide adenine dinucleotide analogues." J Med Chem 50. 23 (2007): 5743-51.

Gladysheva, I. P., Sazonova, I. Y., Houng, A., Hedstrom, L., Reed, G. L.. "Regulation of nonproteolytic active site formation in plasminogen." Biochemistry 46. 30 (2007): 8879-87.

Liu, L., Mushero, N., Hedstrom, L., Gershenson, A.. "Short-lived protease serpin complexes: partial disruption of the rat trypsin active site." Protein Sci 16. 11 (2007): 2403-11.

Oram, S. W., Ai, J., Pagani, G. M., Hitchens, M. R., Stern, J. A., Eggener, S., Pins, M., Xiao, W., Cai, X., Haleem, R., Jiang, F., Pochapsky, T. C., Hedstrom, L., Wang, Z.. "Expression and function of the human androgen-responsive gene ADI1 in prostate cancer." Neoplasia 9. 8 (2007): 643-51.

Bowne, S. J., Sullivan, L. S., Mortimer, S. E., Hedstrom, L., Zhu, J., Spellicy, C. J., Gire, A. I., Hughbanks-Wheaton, D., Birch, D. G., Lewis, R. A., Heckenlively, J. R., Daiger, S. P.. "Spectrum and frequency of mutations in IMPDH1 associated with autosomal dominant retinitis pigmentosa and leber congenital amaurosis." Invest Ophthalmol Vis Sci 47. 1 (2006): 34-42.

Hedstrom, L., Gan, L.. "IMP dehydrogenase: structural schizophrenia and an unusual base." Curr Opin Chem Biol 10. 5 (2006): 520-5.

Liu, L., Mushero, N., Hedstrom, L., Gershenson, A.. "Conformational distributions of protease-serpin complexes: a partially translocated complex." Biochemistry 45. 36 (2006): 10865-72.

Rejman, D., Olesiak, M., Chen, L., Patterson, S. E., Wilson, D., Jayaram, H. N., Hedstrom, L., Pankiewicz, K. W.. "Novel methylenephosphophosphonate analogues of mycophenolic adenine dinucleotide. Inhibition of inosine monophosphate dehydrogenase." J Med Chem 49. 16 (2006): 5018-22.

Hedstrom,Lizbeth, Guillén Schlippe, Yollete V.. "A Twisted Base? the Role of Arginine in Enzyme-Catalyzed Proton Abstractions." (2005): 266-278.

Hedstrom,Lizbeth, Guillén Schlippe et al. "Substitution of the Conserved Arg-Tyr Dyad Selectively Disrupts the Hydrolysis Phase of the IMP Dehydrogenase Reaction." Biochemistry (2004): 4511-4521.

Hedstrom,Lizbeth, McLean et al. "Inosine 5¿-monophosphate dehydrogenase binds nucleic acids in vitro and in vivo." Biochemical Journal (2004): 243-251.

Hedstrom,Lizbeth, Umejiego et al. "Cryptosporidium parvum IMP Dehydrogenase: Identification of Functional, Structural and Dynamic Properties that can be Exploited for Drug Design." J. Biol. Chem. (2004): 40320-4032.

Hedstrom,Lizbeth, Zhang et al. "Analogs of 1-phospho-2, 2-dihydroxy-3-oxo-5-methylthiopentane, an acyclic intermediate in the methionine salvage pathway: a new preparation and characterization of activity with E1 enolase/phosphatase from Klebsiella oxytoca." Bioorganic and Medicinal Chemistry Letters (2004): 3847-3855.

Hedstrom,Lizbeth. "Multiple gene transfers in the evolution of parasite nucleotide biosynthesis." Proc. Natl. Acad. Sci. USA (2004): 3154-3159.