G I Lepesheva

Summary

Affiliation: Vanderbilt University
Country: USA

Publications

  1. pmc Sterol 14alpha-demethylase (CYP51) as a therapeutic target for human trypanosomiasis and leishmaniasis
    Galina I Lepesheva
    Department of Biochemistry Vanderbilt University, Nashville, TN 37232, USA
    Curr Top Med Chem 11:2060-71. 2011
  2. pmc Crystal Structure of the New Investigational Drug Candidate VT-1598 in Complex with Aspergillus fumigatus Sterol 14α-Demethylase Provides Insights into Its Broad-Spectrum Antifungal Activity.
    Tatiana Y Hargrove
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
    Antimicrob Agents Chemother 61:. 2017
  3. pmc Design or screening of drugs for the treatment of Chagas disease: what shows the most promise?
    Galina I Lepesheva
    Vanderbilt University, Institute for Global Health, School of Medicine, Center for Structural Biology, Department of Biochemistry, 622 RRB, 23rd at Pierce, Nashville, TN 37232, USA 1 615 343 1373 1 615 322 4349
    Expert Opin Drug Discov 8:1479-89. 2013
  4. ncbi request reprint CYP51 from Trypanosoma brucei is obtusifoliol-specific
    Galina I Lepesheva
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146, USA
    Biochemistry 43:10789-99. 2004
  5. pmc Structural basis for conservation in the CYP51 family
    Galina I Lepesheva
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146, USA
    Biochim Biophys Acta 1814:88-93. 2011
  6. ncbi request reprint CYP51 from Trypanosoma cruzi: a phyla-specific residue in the B' helix defines substrate preferences of sterol 14alpha-demethylase
    Galina I Lepesheva
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    J Biol Chem 281:3577-85. 2006
  7. pmc Crystal structures of Trypanosoma brucei sterol 14alpha-demethylase and implications for selective treatment of human infections
    Galina I Lepesheva
    Department of Biochemistry, Vanderbilt University, Nashville, Tennessee 37232, USA
    J Biol Chem 285:1773-80. 2010
  8. ncbi request reprint Biodiversity of CYP51 in trypanosomes
    G I Lepesheva
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Biochem Soc Trans 34:1161-4. 2006
  9. pmc CYP51: A major drug target in the cytochrome P450 superfamily
    Galina I Lepesheva
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232 0146, USA
    Lipids 43:1117-25. 2008
  10. pmc Sterol 14alpha-demethylase as a potential target for antitrypanosomal therapy: enzyme inhibition and parasite cell growth
    Galina I Lepesheva
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232 0146, USA
    Chem Biol 14:1283-93. 2007

Collaborators

Detail Information

Publications23

  1. pmc Sterol 14alpha-demethylase (CYP51) as a therapeutic target for human trypanosomiasis and leishmaniasis
    Galina I Lepesheva
    Department of Biochemistry Vanderbilt University, Nashville, TN 37232, USA
    Curr Top Med Chem 11:2060-71. 2011
    ....
  2. pmc Crystal Structure of the New Investigational Drug Candidate VT-1598 in Complex with Aspergillus fumigatus Sterol 14α-Demethylase Provides Insights into Its Broad-Spectrum Antifungal Activity.
    Tatiana Y Hargrove
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
    Antimicrob Agents Chemother 61:. 2017
    ..potency of VT-1598 and confirming its promise as a broad-spectrum antifungal agent...
  3. pmc Design or screening of drugs for the treatment of Chagas disease: what shows the most promise?
    Galina I Lepesheva
    Vanderbilt University, Institute for Global Health, School of Medicine, Center for Structural Biology, Department of Biochemistry, 622 RRB, 23rd at Pierce, Nashville, TN 37232, USA 1 615 343 1373 1 615 322 4349
    Expert Opin Drug Discov 8:1479-89. 2013
    ....
  4. ncbi request reprint CYP51 from Trypanosoma brucei is obtusifoliol-specific
    Galina I Lepesheva
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146, USA
    Biochemistry 43:10789-99. 2004
    ....
  5. pmc Structural basis for conservation in the CYP51 family
    Galina I Lepesheva
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146, USA
    Biochim Biophys Acta 1814:88-93. 2011
    ....
  6. ncbi request reprint CYP51 from Trypanosoma cruzi: a phyla-specific residue in the B' helix defines substrate preferences of sterol 14alpha-demethylase
    Galina I Lepesheva
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    J Biol Chem 281:3577-85. 2006
    ....
  7. pmc Crystal structures of Trypanosoma brucei sterol 14alpha-demethylase and implications for selective treatment of human infections
    Galina I Lepesheva
    Department of Biochemistry, Vanderbilt University, Nashville, Tennessee 37232, USA
    J Biol Chem 285:1773-80. 2010
    ..The structures shed new light on 14DM functional conservation and open an excellent opportunity for directed design of novel antiparasitic drugs...
  8. ncbi request reprint Biodiversity of CYP51 in trypanosomes
    G I Lepesheva
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Biochem Soc Trans 34:1161-4. 2006
    ....
  9. pmc CYP51: A major drug target in the cytochrome P450 superfamily
    Galina I Lepesheva
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232 0146, USA
    Lipids 43:1117-25. 2008
    ..32-Methylene cyclopropyl lanost-7-enol exhibited selectivity toward TC with 50% cell growth inhibition at 3 microM...
  10. pmc Sterol 14alpha-demethylase as a potential target for antitrypanosomal therapy: enzyme inhibition and parasite cell growth
    Galina I Lepesheva
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232 0146, USA
    Chem Biol 14:1283-93. 2007
    ..The approach developed here can be used for further large-scale search for new CYP51 inhibitors...
  11. ncbi request reprint Folding requirements are different between sterol 14alpha-demethylase (CYP51) from Mycobacterium tuberculosis and human or fungal orthologs
    G I Lepesheva
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146, USA
    J Biol Chem 276:28413-20. 2001
    ..coli is not conserved. Thus, despite similar spatial folds, functionally related but evolutionarily distinct P450s can follow different folding pathways...
  12. ncbi request reprint CYP51--the omnipotent P450
    Galina I Lepesheva
    Department of Biochemistry, 607 Light Hall, Vanderbilt University School of Medicine, Nashville, TN 37232 0146, USA
    Mol Cell Endocrinol 215:165-70. 2004
    ....
  13. pmc Sterol 14alpha-demethylase cytochrome P450 (CYP51), a P450 in all biological kingdoms
    Galina I Lepesheva
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232 0146, USA
    Biochim Biophys Acta 1770:467-77. 2007
    ..Two possible roles of CYP51 in P450 evolution are discussed and the major approaches for CYP51 inhibition are summarized...
  14. pmc Structural insights into inhibition of sterol 14alpha-demethylase in the human pathogen Trypanosoma cruzi
    Galina I Lepesheva
    Department of Biochemistry, School of Medicine, Vanderbilt University, Nashville, Tennessee 37232, USA
    J Biol Chem 285:25582-90. 2010
    ....
  15. pmc Indomethacin amides as a novel molecular scaffold for targeting Trypanosoma cruzi sterol 14alpha-demethylase
    Mary E Konkle
    Department of Chemistry, School of Medicine, Vanderbilt University, Nashville, Tennessee 37232, USA
    J Med Chem 52:2846-53. 2009
    ..Analysis of TC sterol composition indicated that the mode of action of the compounds is by inhibition of sterol biosynthesis in the parasite...
  16. pmc Conformational dynamics in the F/G segment of CYP51 from Mycobacterium tuberculosis monitored by FRET
    Galina I Lepesheva
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232 0146, USA
    Arch Biochem Biophys 464:221-7. 2007
    ..The results confirm (1) functional importance of conformational motions in the MTCYP51 F/G segment and (2) applicability of FRET to monitor them in solution...
  17. ncbi request reprint Sterol 14 alpha-demethylase, an abundant and essential mixed-function oxidase
    Michael R Waterman
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232 0146, USA
    Biochem Biophys Res Commun 338:418-22. 2005
    ..Together these studies provide the most detailed understanding of any single cytochrome P450 and this minireview summarizes this information...
  18. ncbi request reprint Estriol bound and ligand-free structures of sterol 14alpha-demethylase
    Larissa M Podust
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Structure 12:1937-45. 2004
    ..A mechanism for azole resistance in the yeast pathogen Candida albicans associated with mutations in the ERG11 gene encoding CYP51 is suggested based on CYP51 protein dynamics...
  19. ncbi request reprint Fluconazole binding and sterol demethylation in three CYP51 isoforms indicate differences in active site topology
    Aouatef Bellamine
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232 0146, USA
    J Lipid Res 45:2000-7. 2004
    ..Because these three residues align in the three isoforms, the results indicate that their active sites contain important structural differences, and further emphasize that fluconazole and substrate binding are uncoupled properties...
  20. ncbi request reprint Conservation in the CYP51 family. Role of the B' helix/BC loop and helices F and G in enzymatic function
    Galina I Lepesheva
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146, USA
    Biochemistry 42:9091-101. 2003
    ..Mutagenesis of corresponding residues in human CYP51 implies that the conserved amino acids might be essential for the evolutionary conservation of sterol 14 alpha-demethylation from bacteria to mammals...
  21. ncbi request reprint Mechanistic analysis of a multiple product sterol methyltransferase implicated in ergosterol biosynthesis in Trypanosoma brucei
    Wenxu Zhou
    Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas 79409 1064, USA
    J Biol Chem 281:6290-6. 2006
    ....
  22. ncbi request reprint Probing the interaction of bovine cytochrome P450scc (CYP11A1) with adrenodoxin: evaluating site-directed mutations by molecular modeling
    Sergey A Usanov
    Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, 220141, Minsk, Kuprevicha 5 2, Belarus
    Biochemistry 41:8310-20. 2002
    ..Thus, the biochemical and molecular modeling studies together support the hypothesis that K267, K403, K405, and R426 participate in the electrostatic interaction of P450scc with Adx...
  23. ncbi request reprint A second FMN binding site in yeast NADPH-cytochrome P450 reductase suggests a mechanism of electron transfer by diflavin reductases
    David C Lamb
    Wolfson Laboratory of P450 Biodiversity, Swansea Medical School University of Wales Swansea, Swansea, Wales SA2 8PP, UK
    Structure 14:51-61. 2006
    ....