LIZBETH K HEDSTROM

Summary

Affiliation: Brandeis University
Country: USA

Publications

  1. pmc A kinetic alignment of orthologous inosine-5'-monophosphate dehydrogenases
    Thomas V Riera
    Departments of Biochemistry and Chemistry, Brandeis University, Waltham, Massachusetts 02454, USA
    Biochemistry 47:8689-96. 2008
  2. pmc The dynamic determinants of reaction specificity in the IMPDH/GMPR family of (β/α)(8) barrel enzymes
    Lizbeth Hedstrom
    Departments of Biology and Chemistry, Brandeis University, Waltham, MA 02454, USA
    Crit Rev Biochem Mol Biol 47:250-63. 2012
  3. ncbi request reprint Serine protease mechanism and specificity
    Lizbeth Hedstrom
    Department of Biochemistry, MS 009, Brandeis University, Waltham, Massachusetts 02454, USA
    Chem Rev 102:4501-24. 2002
  4. ncbi request reprint The antibiotic potential of prokaryotic IMP dehydrogenase inhibitors
    L Hedstrom
    Brandeis University, Departments of Biology, Waltham, MA 02454 9110, USA
    Curr Med Chem 18:1909-18. 2011
  5. doi request reprint IMP dehydrogenase-linked retinitis pigmentosa
    Lizbeth Hedstrom
    Department of Chemistry, Brandeis University, Waltham, Massachusetts, USA
    Nucleosides Nucleotides Nucleic Acids 27:839-49. 2008
  6. ncbi request reprint IMP dehydrogenase: structural schizophrenia and an unusual base
    Lizbeth Hedstrom
    Department of Biochemistry, Brandeis University, Waltham, MA 02454, USA
    Curr Opin Chem Biol 10:520-5. 2006
  7. ncbi request reprint The immunosuppressive agent mizoribine monophosphate forms a transition state analogue complex with inosine monophosphate dehydrogenase
    Lu Gan
    Department of Biochemistry and Chemistry and the Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts 02454, USA
    Biochemistry 42:857-63. 2003
  8. ncbi request reprint A twisted base? The role of arginine in enzyme-catalyzed proton abstractions
    Yollete V Guillen Schlippe
    Department of Biochemistry, Brandeis University, Waltham, MA 02454, USA
    Arch Biochem Biophys 433:266-78. 2005
  9. pmc Short-lived protease serpin complexes: partial disruption of the rat trypsin active site
    Lu Liu
    Department of Chemistry, Graduate Program in Biochemistry, Brandeis University, Waltham, MA 02454, USA
    Protein Sci 16:2403-11. 2007
  10. pmc Inosine 5'-monophosphate dehydrogenase binds nucleic acids in vitro and in vivo
    Jeremy E McLean
    Program in Biophysics and Structural Biology, Brandeis University, MS 009, 415 South St, Waltham, MA 02454, USA
    Biochem J 379:243-51. 2004

Research Grants

  1. IMP Dehydrogenase
    Lizbeth Hedstrom; Fiscal Year: 2007
  2. Development of IMPDH-Targeted Drugs against Crytosporidium
    Lizbeth Hedstrom; Fiscal Year: 2007
  3. IMP Dehydrogenase
    Lizbeth Hedstrom; Fiscal Year: 2004
  4. IMP Dehydrogenase
    Lizbeth Hedstrom; Fiscal Year: 2004
  5. IMP Dehydrogenase
    Lizbeth Hedstrom; Fiscal Year: 2009
  6. IMP Dehydrogenase
    Lizbeth Hedstrom; Fiscal Year: 2009
  7. The mechanism of IMPDH1-mediated retinitis pigmentosa
    Lizbeth Hedstrom; Fiscal Year: 2007
  8. IMP Dehydrogenase
    Lizbeth Hedstrom; Fiscal Year: 2005
  9. INOSINE MONOPHOSPHATE DEHYDROGENASE
    Lizbeth Hedstrom; Fiscal Year: 2003
  10. INOSINE MONOPHOSPHATE DEHYDROGENASE
    Lizbeth Hedstrom; Fiscal Year: 2001

Collaborators

  • G G Petsko
  • Stephen Daiger
  • Sara J Bowne
  • G D Cuny
  • Wen Wang
  • Yollete V Guillen Schlippe
  • Thomas V Riera
  • Sarah E Mortimer
  • Lu Liu
  • Dong Xu
  • Lu Gan
  • Iain S MacPherson
  • Minjia Zhang
  • Sushil K Maurya
  • Nicole N Benjamin
  • Nwakaso N Umejiego
  • Anne Gershenson
  • Nicole Mushero
  • Nobuko Hamaguchi
  • Jeremy E McLean
  • Mohammad R Seyedsayamdost
  • Suresh Kumar Gorla
  • Sivapriya Kirubakaran
  • J Alejandro D'Aquino
  • Corey R Johnson
  • Shivapriya Kirubakaran
  • Deviprasad R Gollapalli
  • Boris Striepen
  • Anna Volftsun
  • Garrett Cobb
  • Deviprasad Gollapalli
  • Hoong Chuin Lim
  • Dharia McGrew
  • Lisa Sharling
  • Jennifer Lu
  • Catherine J Spellicy
  • Adam H Stroupe
  • Helen R Josephine
  • Peter Belenky
  • Martin Stanton
  • Satoshi Shuto
  • Akira Matsuda

Detail Information

Publications22

  1. pmc A kinetic alignment of orthologous inosine-5'-monophosphate dehydrogenases
    Thomas V Riera
    Departments of Biochemistry and Chemistry, Brandeis University, Waltham, Massachusetts 02454, USA
    Biochemistry 47:8689-96. 2008
    ..This observation suggests that the closure of the flap simply sets the stage for catalysis rather than plays a more active role in the chemical transformation. This work provides the essential mechanistic framework for drug discovery...
  2. pmc The dynamic determinants of reaction specificity in the IMPDH/GMPR family of (β/α)(8) barrel enzymes
    Lizbeth Hedstrom
    Departments of Biology and Chemistry, Brandeis University, Waltham, MA 02454, USA
    Crit Rev Biochem Mol Biol 47:250-63. 2012
    ..Thus reaction specificity is controlled by differences in dynamics, which in turn are controlled by residues outside the active site. These findings have some intriguing implications for the evolution of the IMPDH/GMPR family...
  3. ncbi request reprint Serine protease mechanism and specificity
    Lizbeth Hedstrom
    Department of Biochemistry, MS 009, Brandeis University, Waltham, Massachusetts 02454, USA
    Chem Rev 102:4501-24. 2002
  4. ncbi request reprint The antibiotic potential of prokaryotic IMP dehydrogenase inhibitors
    L Hedstrom
    Brandeis University, Departments of Biology, Waltham, MA 02454 9110, USA
    Curr Med Chem 18:1909-18. 2011
    ..A second generation inhibitor displays antibacterial activity against Helicobacter pylori, demonstrating the antibiotic potential of IMPDH inhibitors...
  5. doi request reprint IMP dehydrogenase-linked retinitis pigmentosa
    Lizbeth Hedstrom
    Department of Chemistry, Brandeis University, Waltham, Massachusetts, USA
    Nucleosides Nucleotides Nucleic Acids 27:839-49. 2008
    ..These observations suggest that IMPDH1 has a previously unappreciated role in RNA metabolism that is crucial for photoreceptor function...
  6. ncbi request reprint IMP dehydrogenase: structural schizophrenia and an unusual base
    Lizbeth Hedstrom
    Department of Biochemistry, Brandeis University, Waltham, MA 02454, USA
    Curr Opin Chem Biol 10:520-5. 2006
    ..How the balance between conformational states is maintained and how the various conformational states interconvert is only beginning to be understood...
  7. ncbi request reprint The immunosuppressive agent mizoribine monophosphate forms a transition state analogue complex with inosine monophosphate dehydrogenase
    Lu Gan
    Department of Biochemistry and Chemistry and the Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts 02454, USA
    Biochemistry 42:857-63. 2003
    ..The closed conformation provides a structural explanation for the differences in drug selectivity and catalytic efficiency of IMPDH isozymes...
  8. ncbi request reprint A twisted base? The role of arginine in enzyme-catalyzed proton abstractions
    Yollete V Guillen Schlippe
    Department of Biochemistry, Brandeis University, Waltham, MA 02454, USA
    Arch Biochem Biophys 433:266-78. 2005
    ..The chemistry of the guanidine group suggests unique strategies to lower the pK(a) of Arg. Lastly, the presumption that general bases must be predominantly deprotonated is revisited...
  9. pmc Short-lived protease serpin complexes: partial disruption of the rat trypsin active site
    Lu Liu
    Department of Chemistry, Graduate Program in Biochemistry, Brandeis University, Waltham, MA 02454, USA
    Protein Sci 16:2403-11. 2007
    ..These results also demonstrate that interactions between target proteases and the body of the serpin can hinder protease translocation leading to short-lived covalent complexes...
  10. pmc Inosine 5'-monophosphate dehydrogenase binds nucleic acids in vitro and in vivo
    Jeremy E McLean
    Program in Biophysics and Structural Biology, Brandeis University, MS 009, 415 South St, Waltham, MA 02454, USA
    Biochem J 379:243-51. 2004
    ..These experiments indicate that IMPDH has a previously unappreciated role in replication, transcription or translation that is mediated by the subdomain...
  11. ncbi request reprint Substitution of the conserved Arg-Tyr dyad selectively disrupts the hydrolysis phase of the IMP dehydrogenase reaction
    Yollete V Guillen Schlippe
    Department of Biochemistry, Brandeis University, Waltham, Massachusetts 02454, USA
    Biochemistry 43:4511-21. 2004
    ..Moreover, since the effects of the Tyr419Phe mutation are comparatively small, these experiments suggest that Arg418 acts as the base to activate water...
  12. ncbi request reprint Crystal structure of a ternary complex of Tritrichomonas foetus inosine 5'-monophosphate dehydrogenase: NAD+ orients the active site loop for catalysis
    Lu Gan
    Department of Biochemistry, Brandeis University, Waltham, Massachusetts 02454, USA
    Biochemistry 41:13309-17. 2002
    ..This site is adjacent to beta-Me-TAD, consistent with the link between the K(+) activation and NAD(+). However, contrary to the coupling model, the flap does not cover the adenosine subsite and remains largely disordered...
  13. pmc Autosomal dominant retinitis pigmentosa mutations in inosine 5'-monophosphate dehydrogenase type I disrupt nucleic acid binding
    Sarah E Mortimer
    Department of Biochemistry, Brandeis University, 415 South St, Waltham, MA 02454 9110, USA
    Biochem J 390:41-7. 2005
    ..These observations suggest that nucleic acid binding provides a functional assay for adRP pathogenicity. The putative adRP-linked mutation V268I also disrupts nucleic acid binding, which suggests that this mutation is indeed pathogenic...
  14. doi request reprint An overview of serine proteases
    Lizbeth Hedstrom
    Brandeis University, Waltham, Massachusetts, USA
    Curr Protoc Protein Sci . 2002
    ..This unit summarizes the families of serine proteases and their mechanism of catalysis. Methods for assays and determining substrate specificity are briefly described. The mode of action of commonly available inhibitors is also included...
  15. ncbi request reprint Is Arg418 the catalytic base required for the hydrolysis step of the IMP dehydrogenase reaction?
    Yollete V Guillen Schlippe
    Department of Biochemistry, Brandeis University, Waltham, Massachusetts 02454, USA
    Biochemistry 44:11700-7. 2005
    ..The simplest explanation for these observations is that Arg418 serves as the base that activates water in the IMPDH reaction...
  16. pmc Targeting a prokaryotic protein in a eukaryotic pathogen: identification of lead compounds against cryptosporidiosis
    Nwakaso N Umejiego
    Department of Biochemistry, Brandeis University, 415 South Street, Waltham, MA 02454, USA
    Chem Biol 15:70-7. 2008
    ..We have identified four parasite-selective IMPDH inhibitors that display antiparasitic activity with greater potency than paromomycin, the current gold standard for anticryptosporidial activity...
  17. pmc Triazole inhibitors of Cryptosporidium parvum inosine 5'-monophosphate dehydrogenase
    Sushil K Maurya
    Department of Biology, Brandeis University, MS009, 415 South Street, Waltham, Massachusetts 02454, USA
    J Med Chem 52:4623-30. 2009
    ..The 1,2,3-triazole CpIMPDH inhibitors provide new tools for elucidating the role of IMPDH in C. parvum and may serve as potential therapeutics for treating cryptosporidiosis...
  18. pmc The structural basis of Cryptosporidium -specific IMP dehydrogenase inhibitor selectivity
    Iain S MacPherson
    Departments of Biology, Brandeis University, MS009, 415 South Street, Waltham, Massachusetts 02454, USA
    J Am Chem Soc 132:1230-1. 2010
    ..Using this information, we have synthesized low-nanomolar inhibitors that display 10(3) selectivity for the parasite enzyme over human IMPDH2...
  19. ncbi request reprint Conformational distributions of protease-serpin complexes: a partially translocated complex
    Lu Liu
    Department of Chemistry, Brandeis University, 415 South Street, Waltham, Massachusetts 02454, USA
    Biochemistry 45:10865-72. 2006
    ..These results highlight the role of protease stability in determining the conformational distributions of protease-serpin covalent complexes and show that full translocation is not required for the formation of metastable complexes...
  20. pmc Retinal isoforms of inosine 5'-monophosphate dehydrogenase type 1 are poor nucleic acid binding proteins
    Dong Xu
    Department of Biochemistry, Brandeis University, 415 South Street, MS 009, Waltham, MA 02454, USA
    Arch Biochem Biophys 472:100-4. 2008
    ..This observation indicates that the C-terminal extension unique to the retinal isoforms blocks the nucleic acid binding site of IMPDH1, and thus uniquely regulates protein function within photoreceptors...
  21. pmc IMP dehydrogenase type 1 associates with polyribosomes translating rhodopsin mRNA
    Sarah E Mortimer
    Department of Biochemistry, Brandeis University, Waltham, Massachusetts 02454 9110, USA
    J Biol Chem 283:36354-60. 2008
    ..We propose that IMPDH coordinates the translation of a set of mRNAs, perhaps by modulating localization or degradation...
  22. ncbi request reprint Guanidine derivatives rescue the Arg418Ala mutation of Tritrichomonas foetus IMP dehydrogenase
    Yollete V Guillen Schlippe
    Department of Biochemistry, Brandeis University, Waltham, Massachusetts 02454, USA
    Biochemistry 44:16695-700. 2005
    ..These results suggest that proton transfer from water to guanidine is almost complete in the transition state...

Research Grants18

  1. IMP Dehydrogenase
    Lizbeth Hedstrom; Fiscal Year: 2007
    ..Elucidation of the function of the CBS domains is critical for the development of chemotherapy of retinitis pigmentosa and other inherited diseases involving CBS domains. ..
  2. Development of IMPDH-Targeted Drugs against Crytosporidium
    Lizbeth Hedstrom; Fiscal Year: 2007
    ..If successful, the work described in this proposal will develop an urgently needed drug for the management of cryptosporidiosis in epidemic outbreaks and AIDS patients that will be invaluable in the event of a bioterrorist attack. ..
  3. IMP Dehydrogenase
    Lizbeth Hedstrom; Fiscal Year: 2004
    ..In addition to being crucial for the design of isozyme-specific inhibitors of IMPDH, this work will be an important contribution to understanding the relationship between structure and function in enzyme catalysis. ..
  4. IMP Dehydrogenase
    Lizbeth Hedstrom; Fiscal Year: 2004
    ..In addition to being crucial for the design of isozyme-specific inhibitors of IMPDH, this work will be an important contribution to understanding the relationship between structure and function in enzyme catalysis. ..
  5. IMP Dehydrogenase
    Lizbeth Hedstrom; Fiscal Year: 2009
    ..Further, these motifs/factors will be new candidates for the 25% of hereditary retinal disease that is currently undefined. ..
  6. IMP Dehydrogenase
    Lizbeth Hedstrom; Fiscal Year: 2009
    ..Elucidation of the function of the CBS domains is critical for the development of chemotherapy of retinitis pigmentosa and other inherited diseases involving CBS domains. ..
  7. The mechanism of IMPDH1-mediated retinitis pigmentosa
    Lizbeth Hedstrom; Fiscal Year: 2007
    ..Lastly, this work will provide important new insights into the biology of IMPDH, an important drug target for immunosuppressive, antiviral and cancer chemotherapy. ..
  8. IMP Dehydrogenase
    Lizbeth Hedstrom; Fiscal Year: 2005
    ..In addition to being crucial for the design of isozyme-specific inhibitors of IMPDH, this work will be an important contribution to understanding the relationship between structure and function in enzyme catalysis. ..
  9. INOSINE MONOPHOSPHATE DEHYDROGENASE
    Lizbeth Hedstrom; Fiscal Year: 2003
    ..In addition to being crucial for the design of isozyme-specific inhibitors of IMPDH, this work will be an important contribution to understanding the relationship between structure and function in enzyme catalysis. ..
  10. INOSINE MONOPHOSPHATE DEHYDROGENASE
    Lizbeth Hedstrom; Fiscal Year: 2001
    ..The structures of IMPDH complexed with inhibitors will also be solved. These experiments will utilize steady state kinetic, pre-steady state kinetic, site-directed mutagenesis and x-ray crystallography. ..
  11. INOSINE MONOPHOSPHATE DEHYDROGENASE
    Lizbeth Hedstrom; Fiscal Year: 2000
    ..The structures of IMPDH complexed with inhibitors will also be solved. These experiments will utilize steady state kinetic, pre-steady state kinetic, site-directed mutagenesis and x-ray crystallography. ..
  12. INOSINE MONOPHOSPHATE DEHYDROGENASE
    Lizbeth Hedstrom; Fiscal Year: 1999
    ..The structures of IMPDH complexed with inhibitors will also be solved. These experiments will utilize steady state kinetic, pre-steady state kinetic, site-directed mutagenesis and x-ray crystallography. ..
  13. IMP Dehydrogenase
    Lizbeth Hedstrom; Fiscal Year: 2006
    ..In addition to being crucial for the design of isozyme-specific inhibitors of IMPDH, this work will be an important contribution to understanding the relationship between structure and function in enzyme catalysis. ..
  14. IMP Dehydrogenase
    LIZBETH K HEDSTROM; Fiscal Year: 2010
    ..Elucidation of the function of the CBS domains is critical for the development of chemotherapy of retinitis pigmentosa and other inherited diseases involving CBS domains. ..