KATHLEEN BERKNER

Summary

Affiliation: Cleveland Clinic Foundation
Country: USA

Publications

  1. ncbi request reprint The physiology of vitamin K nutriture and vitamin K-dependent protein function in atherosclerosis
    K L Berkner
    Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, Cleveland, OH 44195, USA
    J Thromb Haemost 2:2118-32. 2004
  2. ncbi request reprint The vitamin K-dependent carboxylase
    Kathleen L Berkner
    Department of Molecular Cardiology, Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, Lerner Research Institute, Cleveland, Ohio 44195, USA
    Annu Rev Nutr 25:127-49. 2005
  3. pmc Vitamin K-dependent carboxylation of the carboxylase
    K L Berkner
    Lerner Research Institute, Cleveland Clinic Foundation, Department of Molecular Cardiology, OH 44195, USA
    Proc Natl Acad Sci U S A 95:466-71. 1998
  4. ncbi request reprint Identification of sequences within the gamma-carboxylase that represent a novel contact site with vitamin K-dependent proteins and that are required for activity
    B N Pudota
    Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    J Biol Chem 276:46878-86. 2001
  5. ncbi request reprint Tethered processivity of the vitamin K-dependent carboxylase: factor IX is efficiently modified in a mechanism which distinguishes Gla's from Glu's and which accounts for comprehensive carboxylation in vivo
    O Stenina
    Department of Molecular Cardiology, Cleveland Clinic Foundation, 9500 Euclid Avenue, NB50, Cleveland, Ohio 44195, USA
    Biochemistry 40:10301-9. 2001
  6. pmc Identification of the vitamin K-dependent carboxylase active site: Cys-99 and Cys-450 are required for both epoxidation and carboxylation
    B N Pudota
    Department of Molecular Cardiology, Lerner Research Institute, Jacobs Center for Thrombosis and Vascular Biology, Cleveland Clinic Foundation, 9500 Euclid Avenue, NB50, Cleveland, OH 44195, USA
    Proc Natl Acad Sci U S A 97:13033-8. 2000
  7. ncbi request reprint The vitamin K-dependent carboxylase has been acquired by Leptospira pathogens and shows altered activity that suggests a role other than protein carboxylation
    Mark A Rishavy
    Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, Cleveland, Ohio 44195, USA
    J Biol Chem 280:34870-7. 2005
  8. pmc Insight into the coupling mechanism of the vitamin K-dependent carboxylase: mutation of histidine 160 disrupts glutamic acid carbanion formation and efficient coupling of vitamin K epoxidation to glutamic acid carboxylation
    Mark A Rishavy
    Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA
    Biochemistry 47:9836-46. 2008
  9. pmc A new model for vitamin K-dependent carboxylation: the catalytic base that deprotonates vitamin K hydroquinone is not Cys but an activated amine
    Mark A Rishavy
    Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    Proc Natl Acad Sci U S A 101:13732-7. 2004
  10. ncbi request reprint Sir3p phosphorylation by the Slt2p pathway effects redistribution of silencing function and shortened lifespan
    Alo Ray
    Department of Molecular Biology, NC20, Cleveland Clinic Foundation, Lerner Research Institute, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA
    Nat Genet 33:522-6. 2003

Research Grants

  1. Structure-Function Analysis of the Gamma Carboxylase
    KATHLEEN LUCILE BERKNER; Fiscal Year: 2010
  2. Vitamin K Oxidoreductase: function and physiology
    KATHLEEN LUCILE BERKNER; Fiscal Year: 2010
  3. Vitamin K Oxidoreductase: function and physiology
    KATHLEEN BERKNER; Fiscal Year: 2009
  4. Structure-Function Analysis of the Gamma Carboxylase
    KATHLEEN BERKNER; Fiscal Year: 2007
  5. Structure-Function Analysis of the Gamma-Carboxylase
    KATHLEEN BERKNER; Fiscal Year: 2006
  6. Structure-Function Analysis of the Gamma-Carboxylase
    KATHLEEN BERKNER; Fiscal Year: 2003
  7. STRUCTURE/FUNCTION ANALYSIS OF THE GAMMA-CARBOXYLASE
    KATHLEEN BERKNER; Fiscal Year: 2001
  8. Vitamin K Oxidoreductase: function and physiology
    KATHLEEN LUCILE BERKNER; Fiscal Year: 2011

Collaborators

  • Mark A Rishavy
  • Kevin W Hallgren
  • Kurt W Runge
  • Anna V Yakubenko
  • B N Pudota
  • Dhouha Darghouth
  • Rebecca L Shtofman
  • Wen Qian
  • Jee Hyeon Song
  • Alo Ray
  • E L Hommema
  • O Stenina
  • B A McNally
  • K W Hallgren
  • Youssef Gharbi
  • Jean Philippe Rosa
  • Sophie LeRicousse
  • Amel Mrad
  • Ahmed Maherzi
  • Radhia Kastally
  • Richard L Zuerner
  • B Nirmala Pudota
  • Ronald E Hector
  • Nilanjan Roy
  • Eric L Hommema
  • Beth A McNally
  • S Lee
  • K A West
  • J W Crabb
  • K S Misono
  • M Miyagi

Detail Information

Publications15

  1. ncbi request reprint The physiology of vitamin K nutriture and vitamin K-dependent protein function in atherosclerosis
    K L Berkner
    Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, Cleveland, OH 44195, USA
    J Thromb Haemost 2:2118-32. 2004
    ..Recent studies suggest involvement in arterial calcification, which may be influenced by dietary levels of vitamin K and by anticoagulant drugs such as warfarin that antagonize vitamin K action...
  2. ncbi request reprint The vitamin K-dependent carboxylase
    Kathleen L Berkner
    Department of Molecular Cardiology, Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, Lerner Research Institute, Cleveland, Ohio 44195, USA
    Annu Rev Nutr 25:127-49. 2005
    ....
  3. pmc Vitamin K-dependent carboxylation of the carboxylase
    K L Berkner
    Lerner Research Institute, Cleveland Clinic Foundation, Department of Molecular Cardiology, OH 44195, USA
    Proc Natl Acad Sci U S A 95:466-71. 1998
    ..The discovery of carboxylase carboxylation has broad implications for the mechanism of VKD protein carboxylation and Warfarin-based anti-coagulant therapies that need to be considered both retrospectively and in the future...
  4. ncbi request reprint Identification of sequences within the gamma-carboxylase that represent a novel contact site with vitamin K-dependent proteins and that are required for activity
    B N Pudota
    Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    J Biol Chem 276:46878-86. 2001
    ....
  5. ncbi request reprint Tethered processivity of the vitamin K-dependent carboxylase: factor IX is efficiently modified in a mechanism which distinguishes Gla's from Glu's and which accounts for comprehensive carboxylation in vivo
    O Stenina
    Department of Molecular Cardiology, Cleveland Clinic Foundation, 9500 Euclid Avenue, NB50, Cleveland, Ohio 44195, USA
    Biochemistry 40:10301-9. 2001
    ....
  6. pmc Identification of the vitamin K-dependent carboxylase active site: Cys-99 and Cys-450 are required for both epoxidation and carboxylation
    B N Pudota
    Department of Molecular Cardiology, Lerner Research Institute, Jacobs Center for Thrombosis and Vascular Biology, Cleveland Clinic Foundation, 9500 Euclid Avenue, NB50, Cleveland, OH 44195, USA
    Proc Natl Acad Sci U S A 97:13033-8. 2000
    ....
  7. ncbi request reprint The vitamin K-dependent carboxylase has been acquired by Leptospira pathogens and shows altered activity that suggests a role other than protein carboxylation
    Mark A Rishavy
    Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, Cleveland, Ohio 44195, USA
    J Biol Chem 280:34870-7. 2005
    ....
  8. pmc Insight into the coupling mechanism of the vitamin K-dependent carboxylase: mutation of histidine 160 disrupts glutamic acid carbanion formation and efficient coupling of vitamin K epoxidation to glutamic acid carboxylation
    Mark A Rishavy
    Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA
    Biochemistry 47:9836-46. 2008
    ..His160 is highly conserved in metazoan VKD carboxylases but not in some bacterial orthologues (acquired by horizontal gene transfer), which has implications for how bacteria have adapted the carboxylase for novel functions...
  9. pmc A new model for vitamin K-dependent carboxylation: the catalytic base that deprotonates vitamin K hydroquinone is not Cys but an activated amine
    Mark A Rishavy
    Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    Proc Natl Acad Sci U S A 101:13732-7. 2004
    ..The identity of the catalytic base is critical to understanding carboxylase mechanism and this work will therefore impact both reinterpretation of previous studies and future ones that define how this important enzyme functions...
  10. ncbi request reprint Sir3p phosphorylation by the Slt2p pathway effects redistribution of silencing function and shortened lifespan
    Alo Ray
    Department of Molecular Biology, NC20, Cleveland Clinic Foundation, Lerner Research Institute, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA
    Nat Genet 33:522-6. 2003
    ..Lifespan extension occurs by a mechanism that is independent of suppressing rDNA recombination. Thus, Slt2p is an enzymatic regulator of silencing function that couples commitment to cell growth and shorter lifespan...
  11. ncbi request reprint Carboxylase overexpression effects full carboxylation but poor release and secretion of factor IX: implications for the release of vitamin K-dependent proteins
    Kevin W Hallgren
    Department of Molecular Cardiology, Lerner Research Institute, Cleveland, Ohio 44195, USA
    Biochemistry 41:15045-55. 2002
    ..The results suggest that the vitamin K cofactor may be limiting for carboxylation in the cell lines...
  12. pmc r-VKORC1 expression in factor IX BHK cells increases the extent of factor IX carboxylation but is limited by saturation of another carboxylation component or by a shift in the rate-limiting step
    Kevin W Hallgren
    Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA
    Biochemistry 45:5587-98. 2006
    ..The studies illustrate the complexity of carboxylation and potential importance of component stoichiometry to overall efficiency...
  13. pmc Compound heterozygosity of novel missense mutations in the gamma-glutamyl-carboxylase gene causes hereditary combined vitamin K-dependent coagulation factor deficiency
    Dhouha Darghouth
    Laboratory of Hemostasis and Thrombosis, U689 INSERM, Hopital Lariboisiere, 41 Boulevard de la Chapelle, 75475 Paris Cedex 10, France
    Blood 108:1925-31. 2006
    ..The implications for carboxylase mechanism are discussed...
  14. ncbi request reprint Brønsted analysis reveals Lys218 as the carboxylase active site base that deprotonates vitamin K hydroquinone to initiate vitamin K-dependent protein carboxylation
    Mark A Rishavy
    Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA
    Biochemistry 45:13239-48. 2006
    ....
  15. doi request reprint Vitamin K-dependent carboxylation
    Kathleen L Berkner
    Department of Molecular Cardiology, Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, Lerner Research Institute, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA
    Vitam Horm 78:131-56. 2008
    ..Also discussed is the role of the carboxylase in mammals and lower organisms, including the bacterial pathogen Leptospira interrogans that has acquired a VKD carboxylase by horizontal transfer...

Research Grants17

  1. Structure-Function Analysis of the Gamma Carboxylase
    KATHLEEN LUCILE BERKNER; Fiscal Year: 2010
    ..The studies will impact the development of anticoagulants and the production of therapeutic proteins for treating hemophilia and septic shock. ..
  2. Vitamin K Oxidoreductase: function and physiology
    KATHLEEN LUCILE BERKNER; Fiscal Year: 2010
    ....
  3. Vitamin K Oxidoreductase: function and physiology
    KATHLEEN BERKNER; Fiscal Year: 2009
    ....
  4. Structure-Function Analysis of the Gamma Carboxylase
    KATHLEEN BERKNER; Fiscal Year: 2007
    ..The studies will impact the development of anticoagulants and the production of therapeutic proteins for treating hemophilia and septic shock. ..
  5. Structure-Function Analysis of the Gamma-Carboxylase
    KATHLEEN BERKNER; Fiscal Year: 2006
    ..abstract_text> ..
  6. Structure-Function Analysis of the Gamma-Carboxylase
    KATHLEEN BERKNER; Fiscal Year: 2003
    ....
  7. STRUCTURE/FUNCTION ANALYSIS OF THE GAMMA-CARBOXYLASE
    KATHLEEN BERKNER; Fiscal Year: 2001
    ..These experiments will also provide methods for the future isolation of VKD proteins and information for the design of anticoagulants that specifically alter hemostasis. ..
  8. Vitamin K Oxidoreductase: function and physiology
    KATHLEEN LUCILE BERKNER; Fiscal Year: 2011
    ....