LORENA BEESE

Summary

Affiliation: Duke University Medical Center
Country: USA

Publications

  1. ncbi request reprint Error-prone replication of oxidatively damaged DNA by a high-fidelity DNA polymerase
    Gerald W Hsu
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    Nature 431:217-21. 2004
  2. pmc Ligand-induced conformational changes in a thermophilic ribose-binding protein
    Matthew J Cuneo
    The Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    BMC Struct Biol 8:50. 2008
  3. ncbi request reprint Reaction path of protein farnesyltransferase at atomic resolution
    Stephen B Long
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    Nature 419:645-50. 2002
  4. ncbi request reprint Crystallographic analysis of CaaX prenyltransferases complexed with substrates defines rules of protein substrate selectivity
    T Scott Reid
    Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA
    J Mol Biol 343:417-33. 2004
  5. ncbi request reprint Crystal structures of the anticancer clinical candidates R115777 (Tipifarnib) and BMS-214662 complexed with protein farnesyltransferase suggest a mechanism of FTI selectivity
    T Scott Reid
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    Biochemistry 43:6877-84. 2004
  6. pmc Structural analysis of semi-specific oligosaccharide recognition by a cellulose-binding protein of thermotoga maritima reveals adaptations for functional diversification of the oligopeptide periplasmic binding protein fold
    Matthew J Cuneo
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 284:33217-23. 2009
  7. ncbi request reprint Crystallographic analysis reveals that anticancer clinical candidate L-778,123 inhibits protein farnesyltransferase and geranylgeranyltransferase-I by different binding modes
    T Scott Reid
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    Biochemistry 43:9000-8. 2004
  8. doi request reprint Structural adaptations that modulate monosaccharide, disaccharide, and trisaccharide specificities in periplasmic maltose-binding proteins
    Matthew J Cuneo
    Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA
    J Mol Biol 389:157-66. 2009
  9. ncbi request reprint Conversion of protein farnesyltransferase to a geranylgeranyltransferase
    Kimberly L Terry
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    Biochemistry 45:9746-55. 2006
  10. pmc Structural basis for binding and selectivity of antimalarial and anticancer ethylenediamine inhibitors to protein farnesyltransferase
    Michael A Hast
    Department of Biochemistry, Duke University Medical Center, Box 3711, Durham, NC 27710, USA
    Chem Biol 16:181-92. 2009

Collaborators

  • Matthew J Cuneo
  • PAUL LAWRENCE MODRICH
  • Birte Höcker
  • Said M Sebti
  • M H Gelb
  • Wesley C Van Voorhis
  • T Carell
  • Ian M Bell
  • Robert B Lobell
  • Kohei Yokoyama
  • T Scott Reid
  • Michael A Hast
  • Joshua J Warren
  • Kimberly L Terry
  • Gerald W Hsu
  • Ravi R Iyer
  • Patrick J Casey
  • Jeffrey S Taylor
  • Stephen B Long
  • Anita Changela
  • Richard T Eastman
  • Yaji Tian
  • Kimberly T Lane
  • Sean J Johnson
  • S Jane deSolms
  • Miaw Sheue Tsai
  • Jochen Genschel
  • Anna Pluciennik
  • Steven Fletcher
  • Andrew D Hamilton
  • Erin E Pusateri
  • Christopher G Cummings
  • Michelle A Blaskovich
  • Kasey Rivas
  • John White
  • Homme W Hellinga
  • Pradipsinh K Rathod
  • Timothy J Pohlhaus
  • Christophe L M J Verlinde
  • Oliver Hucke
  • Lawrence J Forsberg
  • Natalia P Luneva
  • Nicholas E Geacintov
  • Xuanwei Huang
  • Matthias Ober
  • Christine Fernandes
  • Suzanne C MacTough
  • Carolyn A Buser
  • Hans E Huber
  • Terrence M Ciccarone
  • Nancy N Tsou
  • Michelle Ellis-Hutchings
  • Samuel L Graham
  • Nancy E Kohl
  • Eileen S Walsh
  • Kelly A Hamilton
  • Ronald G Robinson
  • Anthony W Shaw

Detail Information

Publications24

  1. ncbi request reprint Error-prone replication of oxidatively damaged DNA by a high-fidelity DNA polymerase
    Gerald W Hsu
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    Nature 431:217-21. 2004
    ....
  2. pmc Ligand-induced conformational changes in a thermophilic ribose-binding protein
    Matthew J Cuneo
    The Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    BMC Struct Biol 8:50. 2008
    ....
  3. ncbi request reprint Reaction path of protein farnesyltransferase at atomic resolution
    Stephen B Long
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    Nature 419:645-50. 2002
    ..Finally, known FTase inhibitors seem to differ in their mechanism of inhibiting the enzyme...
  4. ncbi request reprint Crystallographic analysis of CaaX prenyltransferases complexed with substrates defines rules of protein substrate selectivity
    T Scott Reid
    Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA
    J Mol Biol 343:417-33. 2004
    ....
  5. ncbi request reprint Crystal structures of the anticancer clinical candidates R115777 (Tipifarnib) and BMS-214662 complexed with protein farnesyltransferase suggest a mechanism of FTI selectivity
    T Scott Reid
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    Biochemistry 43:6877-84. 2004
    ....
  6. pmc Structural analysis of semi-specific oligosaccharide recognition by a cellulose-binding protein of thermotoga maritima reveals adaptations for functional diversification of the oligopeptide periplasmic binding protein fold
    Matthew J Cuneo
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 284:33217-23. 2009
    ..Semi-specific recognition, in which a molecular class rather than individual species is selected, provides an efficient solution for the uptake of complex mixtures...
  7. ncbi request reprint Crystallographic analysis reveals that anticancer clinical candidate L-778,123 inhibits protein farnesyltransferase and geranylgeranyltransferase-I by different binding modes
    T Scott Reid
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    Biochemistry 43:9000-8. 2004
    ..These structures should facilitate the design of more specific inhibitors toward FTase or GGTase-I. Finally, the binding of a drug and anion together could be applicable for developing new classes of inhibitors...
  8. doi request reprint Structural adaptations that modulate monosaccharide, disaccharide, and trisaccharide specificities in periplasmic maltose-binding proteins
    Matthew J Cuneo
    Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA
    J Mol Biol 389:157-66. 2009
    ..We provide a model in which the energetics of long-range conformational equilibria controls subsite occupancy and ligand binding...
  9. ncbi request reprint Conversion of protein farnesyltransferase to a geranylgeranyltransferase
    Kimberly L Terry
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    Biochemistry 45:9746-55. 2006
    ....
  10. pmc Structural basis for binding and selectivity of antimalarial and anticancer ethylenediamine inhibitors to protein farnesyltransferase
    Michael A Hast
    Department of Biochemistry, Duke University Medical Center, Box 3711, Durham, NC 27710, USA
    Chem Biol 16:181-92. 2009
    ..Comparison to a homology model constructed for the P. falciparum FTase suggests opportunities for further improving selectivity of a new generation of antimalarial inhibitors...
  11. pmc Structure of protein geranylgeranyltransferase-I from the human pathogen Candida albicans complexed with a lipid substrate
    Michael A Hast
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 283:31933-40. 2008
    ..These differences indicate the regions where specific protein prenyltransferase inhibitors with antifungal activity can be designed...
  12. ncbi request reprint The crystal structure of a thermophilic glucose binding protein reveals adaptations that interconvert mono and di-saccharide binding sites
    Matthew J Cuneo
    The Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA
    J Mol Biol 362:259-70. 2006
    ..Comparison of ttGBP and MBP provides a clear example of structural adaptations by which the size of ligand binding sites can be controlled in the PBP super family...
  13. pmc Structural analysis of a periplasmic binding protein in the tripartite ATP-independent transporter family reveals a tetrameric assembly that may have a role in ligand transport
    Matthew J Cuneo
    Department of Biochemistry, Duke University, Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 283:32812-20. 2008
    ....
  14. ncbi request reprint Thematic review series: lipid posttranslational modifications. Structural biology of protein farnesyltransferase and geranylgeranyltransferase type I
    Kimberly T Lane
    Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA
    J Lipid Res 47:681-99. 2006
    ..Such complexes may assist in the design of inhibitors that could lead to treatments for cancer, viral infection, and a number of deadly parasitic diseases...
  15. pmc Structure of mammalian protein geranylgeranyltransferase type-I
    Jeffrey S Taylor
    Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA
    EMBO J 22:5963-74. 2003
    ..Understanding these key features of specificity is expected to contribute to optimization of anti-cancer and anti-parasite drugs...
  16. pmc Structure-based design of robust glucose biosensors using a Thermotoga maritima periplasmic glucose-binding protein
    Yaji Tian
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    Protein Sci 16:2240-50. 2007
    ..The immobilized protein retains its response after long-term storage at room temperature...
  17. pmc The structural basis for the mutagenicity of O(6)-methyl-guanine lesions
    Joshua J Warren
    Department of Biochemistry, Duke University Medical Center, Box 3711, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 103:19701-6. 2006
    ..Because DNA methylators constitute an important class of chemotherapeutic agents, the molecular mechanisms of replication of these DNA lesions are important for our understanding of both the genesis and treatment of cancer...
  18. ncbi request reprint Structure of the human MutSalpha DNA lesion recognition complex
    Joshua J Warren
    Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA
    Mol Cell 26:579-92. 2007
    ..This study also allows rigorous mapping of cancer-causing mutations and furthermore suggests structural pathways for allosteric communication between different regions within the heterodimer...
  19. pmc Processive DNA synthesis observed in a polymerase crystal suggests a mechanism for the prevention of frameshift mutations
    Sean J Johnson
    Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 100:3895-900. 2003
    ....
  20. pmc MutLalpha and proliferating cell nuclear antigen share binding sites on MutSbeta
    Ravi R Iyer
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 285:11730-9. 2010
    ..These findings also indicate that MutSbeta- and MutSalpha-initiated repair events differ in fundamental ways...
  21. ncbi request reprint Structure of a high fidelity DNA polymerase bound to a benzo[a]pyrene adduct that blocks replication
    Gerald W Hsu
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 280:3764-70. 2005
    ..The disruptions revealed by the structure of Bacillus fragment bound to a BP adduct provide a molecular basis for rationalizing the potent blocking effect on replication exerted by BP adducts...
  22. ncbi request reprint Dual protein farnesyltransferase-geranylgeranyltransferase-I inhibitors as potential cancer chemotherapeutic agents
    S Jane deSolms
    Departments of Medicinal Chemistry and Cancer Research, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    J Med Chem 46:2973-84. 2003
    ..These compounds are the first reported to inhibit the prenylation of the important oncogene Ki-Ras4B in vivo. Unfortunately, doses sufficient to achieve this endpoint were rapidly lethal...
  23. ncbi request reprint 3-Aminopyrrolidinone farnesyltransferase inhibitors: design of macrocyclic compounds with improved pharmacokinetics and excellent cell potency
    Ian M Bell
    Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA
    J Med Chem 45:2388-409. 2002
    ..Optimization of this 3-aminopyrrolidinone series of compounds led to significant increases in potency, providing 83 and 85, the most potent inhibitors of FTase in cells described to date...
  24. pmc Resistance mutations at the lipid substrate binding site of Plasmodium falciparum protein farnesyltransferase
    Richard T Eastman
    Department of Pathobiology, University of Washington, Seattle, WA 98195 7185, USA
    Mol Biochem Parasitol 152:66-71. 2007
    ..These data provide further support that PFT is the target of THQ inhibitors in P. falciparum and suggest that PFT inhibitors should be combined with other antimalarial agents to minimize the development of resistant parasites...

Research Grants11

  1. STRUCTURE AND MECHANISM OF PROTEIN PRENYLTRANSFERASES
    LORENA BEESE; Fiscal Year: 2007
    ..These structures are expected to facilitate drug development efforts towards highly specific FTIs (and GTIs) and provide insight for development of inhibitors to human pathogens. ..
  2. Structural biology of human DNA mismatch repair machinery
    LORENA BEESE; Fiscal Year: 2009
    ..Together the aims will contribute to furthering our understanding of the molecular basis of MMR-associated human diseases. ..
  3. STRUCTURE AND MECHANISM OF PROTEIN PRENYLTRANSFERASES
    LORENA BEESE; Fiscal Year: 2002
    ..abstract_text> ..