carbon carbon ligases

Summary

Summary: Enzymes that catalyze the joining of two molecules by the formation of a carbon-carbon bond. These are the carboxylating enzymes and are mostly biotinyl-proteins. EC 6.4.

Top Publications

  1. ncbi The inhibitory effect of calumenin on the vitamin K-dependent gamma-carboxylation system. Characterization of the system in normal and warfarin-resistant rats
    Nadeem Wajih
    Departments of Internal Medicine and Biochemistry, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, USA
    J Biol Chem 279:25276-83. 2004
  2. ncbi Kinetic and structural analysis of a new group of Acyl-CoA carboxylases found in Streptomyces coelicolor A3(2)
    Lautaro Diacovich
    Instituto de Biología Molecular y Celular de Rosario IBR Consejo Nacional de Investigaciones Científicas y Técnicas and Departamento de Microbiología, Universidad Nacional de Rosario, Suipaccha 531, 2000 Rosario, Argentina
    J Biol Chem 277:31228-36. 2002
  3. pmc Identification and characterization of Rv3281 as a novel subunit of a biotin-dependent acyl-CoA Carboxylase in Mycobacterium tuberculosis H37Rv
    Tae Jin Oh
    Burnett College of Biomedical Sciences, University of Central Florida, Orlando, 32816, USA
    J Biol Chem 281:3899-908. 2006
  4. ncbi Cloning and expression of the cDNA for human gamma-glutamyl carboxylase
    S M Wu
    Department of Biology, University of North Carolina, Chapel Hill 27599 3280
    Science 254:1634-6. 1991
  5. 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
  6. ncbi Immunocytochemical localization of 3-methylcrotonyl-CoA carboxylase in cultured ependymal, microglial and oligodendroglial cells
    Radovan Murin
    Interfaculty Institute for Biochemistry, University of Tuebingen, Tuebingen, Germany
    J Neurochem 97:1393-402. 2006
  7. ncbi Genetic and biochemical characterization of the alpha and beta components of a propionyl-CoA carboxylase complex of Streptomyces coelicolor A3(2)
    E Rodriguez
    Departamento de Microbiologia, Facultad de Ciencias Bioquimicas y Farmaceuticas, Universidad Nacional de Rosario, Argentina
    Microbiology 145:3109-19. 1999
  8. ncbi Congenital deficiency of vitamin K dependent coagulation factors in two families presents as a genetic defect of the vitamin K-epoxide-reductase-complex
    J Oldenburg
    Institute of Human Genetics, University of Wurzburg, Biozentrum, Germany
    Thromb Haemost 84:937-41. 2000
  9. pmc Structure-based inhibitor design of AccD5, an essential acyl-CoA carboxylase carboxyltransferase domain of Mycobacterium tuberculosis
    Ting Wan Lin
    Department of Molecular Biology and Biochemistry, University of California, Irvine, 92697, USA
    Proc Natl Acad Sci U S A 103:3072-7. 2006
  10. pmc Role of an essential acyl coenzyme A carboxylase in the primary and secondary metabolism of Streptomyces coelicolor A3(2)
    E Rodriguez
    Instituto de Biología Molecular y Celular de Rosario and Departamento de Microbiología, Facultad de Ciencias Bioquimicas y Farmaceuticas, Universidad Nacional de Rosario, Suipacha 531, 2000 Rosario, Argentina
    Appl Environ Microbiol 67:4166-76. 2001

Research Grants

  1. VITAMIN K, METABOLISM AND FUNCTION
    Reidar Wallin; Fiscal Year: 2001
  2. Vitamin K, Bone, and Arterial Calcification
    Reidar Wallin; Fiscal Year: 2006
  3. Structure-Function Analysis of the Gamma-Carboxylase
    KATHLEEN BERKNER; Fiscal Year: 2003
  4. LUNG TRANSCRIPTION FACTOR, LKLF-1
    Jerry Lingrel; Fiscal Year: 2000
  5. STRUCTURE/FUNCTION ANALYSIS OF THE GAMMA-CARBOXYLASE
    KATHLEEN BERKNER; Fiscal Year: 2001
  6. Molecular Genetics of Familial Tumoral Calcinosis
    Jouni Uitto; Fiscal Year: 2009
  7. HMGB1/2 and Cellular Response to Fraudulent Nucleosides
    Evgeny Krynetskiy; Fiscal Year: 2007
  8. COLLAGEN BIOSYNTHESIS OF CULTURED FIBROBLASTS
    Jouni Uitto; Fiscal Year: 2006
  9. Biotin Status in Pregnancy
    Donald M Mock; Fiscal Year: 2010
  10. 12th International Symposium on Basement Membranes
    Jouni Uitto; Fiscal Year: 2005

Scientific Experts

Detail Information

Publications124 found, 100 shown here

  1. ncbi The inhibitory effect of calumenin on the vitamin K-dependent gamma-carboxylation system. Characterization of the system in normal and warfarin-resistant rats
    Nadeem Wajih
    Departments of Internal Medicine and Biochemistry, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, USA
    J Biol Chem 279:25276-83. 2004
    ..Furthermore, the sequence of the 18-kDa subunit 1 of the VKOR enzyme complex was found to be identical in the two rat strains. This finding supports the notion that different forms of genetic warfarin resistance exist...
  2. ncbi Kinetic and structural analysis of a new group of Acyl-CoA carboxylases found in Streptomyces coelicolor A3(2)
    Lautaro Diacovich
    Instituto de Biología Molecular y Celular de Rosario IBR Consejo Nacional de Investigaciones Científicas y Técnicas and Departamento de Microbiología, Universidad Nacional de Rosario, Suipaccha 531, 2000 Rosario, Argentina
    J Biol Chem 277:31228-36. 2002
    ..The epsilon subunit has been found genetically linked to several carboxyltransferases of different Streptomyces species; we propose that this subunit reflects a distinctive characteristic of a new group of acyl-CoA carboxylases...
  3. pmc Identification and characterization of Rv3281 as a novel subunit of a biotin-dependent acyl-CoA Carboxylase in Mycobacterium tuberculosis H37Rv
    Tae Jin Oh
    Burnett College of Biomedical Sciences, University of Central Florida, Orlando, 32816, USA
    J Biol Chem 281:3899-908. 2006
    ..The Rv3281 open reading frame is co-transcribed with Rv3280 in the mycobacterial cell, and the level of epsilon-protein was highest during the log phase and decreased during the stationary phase...
  4. ncbi Cloning and expression of the cDNA for human gamma-glutamyl carboxylase
    S M Wu
    Department of Biology, University of North Carolina, Chapel Hill 27599 3280
    Science 254:1634-6. 1991
    ..3 percent identity with soybean seed lipoxygenase. Expression of the cloned cDNA resulted in an increase in carboxylase activity in microsomes of transfected cells compared to mock-transfected cells...
  5. 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...
  6. ncbi Immunocytochemical localization of 3-methylcrotonyl-CoA carboxylase in cultured ependymal, microglial and oligodendroglial cells
    Radovan Murin
    Interfaculty Institute for Biochemistry, University of Tuebingen, Tuebingen, Germany
    J Neurochem 97:1393-402. 2006
    ..The ubiquitous expression of MCC in glial cells demonstrates the ability of the cells to engage in the catabolism of leucine transported into the brain, mainly for the generation of energy...
  7. ncbi Genetic and biochemical characterization of the alpha and beta components of a propionyl-CoA carboxylase complex of Streptomyces coelicolor A3(2)
    E Rodriguez
    Departamento de Microbiologia, Facultad de Ciencias Bioquimicas y Farmaceuticas, Universidad Nacional de Rosario, Argentina
    Microbiology 145:3109-19. 1999
    ..The fact that accA2 mutants appear to be inviable suggests that this gene encodes a biotinylated protein that might be shared with other carboxyl transferases essential for the growth of S. coelicolor...
  8. ncbi Congenital deficiency of vitamin K dependent coagulation factors in two families presents as a genetic defect of the vitamin K-epoxide-reductase-complex
    J Oldenburg
    Institute of Human Genetics, University of Wurzburg, Biozentrum, Germany
    Thromb Haemost 84:937-41. 2000
    ..Further genetic analysis of such families will provide the basis for a more detailed understanding of the structure-function relation of the enzymes involved in vitamin K metabolism...
  9. pmc Structure-based inhibitor design of AccD5, an essential acyl-CoA carboxylase carboxyltransferase domain of Mycobacterium tuberculosis
    Ting Wan Lin
    Department of Molecular Biology and Biochemistry, University of California, Irvine, 92697, USA
    Proc Natl Acad Sci U S A 103:3072-7. 2006
    ....
  10. pmc Role of an essential acyl coenzyme A carboxylase in the primary and secondary metabolism of Streptomyces coelicolor A3(2)
    E Rodriguez
    Instituto de Biología Molecular y Celular de Rosario and Departamento de Microbiología, Facultad de Ciencias Bioquimicas y Farmaceuticas, Universidad Nacional de Rosario, Suipacha 531, 2000 Rosario, Argentina
    Appl Environ Microbiol 67:4166-76. 2001
    ....
  11. ncbi Crystal structure of the beta-subunit of acyl-CoA carboxylase: structure-based engineering of substrate specificity
    Lautaro Diacovich
    Departamento de Microbiologia, Facultad de Ciencias Bioquimicas y Farmaceuticas, Universidad Nacional de Rosario, Suipacha 531, 2000 Rosario, Argentina
    Biochemistry 43:14027-36. 2004
    ..Our findings enable bioengineering of the acyl-CoA carboxylase (ACCase) substrate specificity to provide novel extender units for the combinatorial biosynthesis of polyketides...
  12. ncbi Genomic sequence and transcription start site for the human gamma-glutamyl carboxylase
    S M Wu
    Department of Biology, University of North Carolina Chapel Hill, 27599 3280, USA
    Blood 89:4058-62. 1997
    ..There are two major transcripts in all tissues examined. They are distinguished by the presence of an Alu sequence in the 3' nontranslated end of the longer species. Relative mRNA levels for 12 bovine tissues are presented...
  13. ncbi The vitamin K-dependent carboxylase
    Steven R Presnell
    Department of Biology, University of North Carolina Chapel Hill, 27599 3280, USA
    Thromb Haemost 87:937-46. 2002
  14. ncbi Compound heterozygous mutations in the gamma-glutamyl carboxylase gene cause combined deficiency of all vitamin K-dependent blood coagulation factors
    Simone Rost
    Institute of Human Genetics, University Wurzburg, Wurzburg, Germany
    Br J Haematol 126:546-9. 2004
    ..Substitution of vitamin K could only partially normalize the levels of coagulation factors. It is suggested that the missense mutation affects either the propeptide binding site or the vitamin K binding site of GGCX...
  15. pmc Familial deficiency of vitamin K-dependent clotting factors
    B W Weston
    The Harold R Roberts Comprehensive Hemophilia Treatment Center, Department of Pediatrics, Division of Hematology Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7220, USA
    Haemophilia 14:1209-13. 2008
    ..The results may also provide potential targets for molecular therapeutics and pharmacogenetics...
  16. doi Novel splice site mutations in the gamma glutamyl carboxylase gene in a child with congenital combined deficiency of the vitamin K-dependent coagulation factors (VKCFD)
    Ruetima Titapiwatanakun
    Division of Pediatric Hematology Oncology, Mayo Clinic, Rochester, Minnesota 55905, USA
    Pediatr Blood Cancer 53:92-5. 2009
    ..Oral vitamin K supplementation resulted in partial resolution of proteins and complete resolution of bleeding...
  17. ncbi Founder mutation Arg485Pro led to recurrent compound heterozygous GGCX genotypes in two German patients with VKCFD type 1
    Simone Rost
    Institute of Human Genetics, Biocenter, Am Hubland, University Wurzburg, Wurzburg, Germany
    Blood Coagul Fibrinolysis 17:503-7. 2006
    ..The founder mutation explains that the only two compound heterozygous VKCFD type 1 patients known today originated from Germany...
  18. ncbi The acyl-AMP ligase FadD32 and AccD4-containing acyl-CoA carboxylase are required for the synthesis of mycolic acids and essential for mycobacterial growth: identification of the carboxylation product and determination of the acyl-CoA carboxylase componen
    Damien Portevin
    Département Mécanismes Moléculaires des Infections Mycobactériennes, Institut de Pharmacologie et Biologie Structurale, CNRS and Université Paul Sabatier Unité Mixte de Recherche 5089, 205 route de Narbonne, 31077 Toulouse Cedex, France
    J Biol Chem 280:8862-74. 2005
    ..smegmatis. Thus, in addition to Pks13, FadD32 and AccD4 are promising targets for the development of new antimicrobial drugs against pathogenic species of mycobacteria and related microorganisms...
  19. pmc Isolated 3-methylcrotonyl-CoA carboxylase deficiency: evidence for an allele-specific dominant negative effect and responsiveness to biotin therapy
    Matthias R Baumgartner
    Division of Metabolism and Molecular Pediatrics, University Children s Hospital, Zurich, Switzerland
    Am J Hum Genet 75:790-800. 2004
    ..We show that MCCA-R385S, but not other MCCA missense alleles, reduces the MCC activity of cotransfected MCCA-wild-type allele. Our results suggest that MCCA-R385S is a dominant negative allele and is biotin responsive in vivo...
  20. ncbi 3-methylcrotonyl-CoA carboxylase deficiency and severe multiple sclerosis
    Niklas Darin
    Department of Pediatrics, Sahlgrenska University Hospital, Goteborg, Sweden
    Pediatr Neurol 36:132-4. 2007
    ..Treatment with steroids had initially a good therapeutic effect on the relapses. The response to interferon beta-1a treatment was poor. On mitoxantrone treatment there was a considerable neurologic recovery...
  21. ncbi A functional single nucleotide polymorphism in the vitamin-K-dependent gamma-glutamyl carboxylase gene (Arg325Gln) is associated with bone mineral density in elderly Japanese women
    Hiroyuki Kinoshita
    Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, Japan
    Bone 40:451-6. 2007
    ..650+/-0.883, mean+/-SD) than those with 325-Arg/Gln or 325-Arg (0.133+/-0.650) (p=0.0383). This is the first report to demonstrate the different activities of GGCX between the common genotypes and their association with BMD...
  22. ncbi Chemical modification of cysteine residues is a misleading indicator of their status as active site residues in the vitamin K-dependent gamma-glutamyl carboxylation reaction
    Jian Ke Tie
    Departments of Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    J Biol Chem 279:54079-87. 2004
    ..We conclude that cysteine residues are not directly involved in carboxylase catalysis, but chemical modification of Cys(323) and Cys(343) may disrupt the three-dimensional structure, resulting in inactivation...
  23. 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...
  24. doi 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...
  25. ncbi Glucocorticoid effects on vitamin K-dependent carboxylase activity and matrix Gla protein expression in rat lung
    Kirk A Gilbert
    Dept of Cellular and Molecular Physiology, H 166, The Pennsylvania State Univ College of Medicine, 500 Univ Dr, Hershey, PA 17033, USA
    Am J Physiol Lung Cell Mol Physiol 285:L569-77. 2003
    ..We propose that glucocorticoids are important regulators of vitamin K function in the developing and adult lung...
  26. pmc Transmembrane domain interactions and residue proline 378 are essential for proper structure, especially disulfide bond formation, in the human vitamin K-dependent gamma-glutamyl carboxylase
    Jian Ke Tie
    Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Biochemistry 47:6301-10. 2008
    ..This latter interaction may be mediated at least in part by a motif of glycine residues in the second transmembrane domain...
  27. ncbi Familial multiple coagulation factor deficiencies: new biologic insight from rare genetic bleeding disorders
    B Zhang
    Department of Internal Medicine and Human Genetics, University of Michigan, Ann Arbor, MI 48109 0650, USA
    J Thromb Haemost 2:1564-72. 2004
    ..The multiple coagulation factor deficiencies provide a notable example of important basic biological insight gained through the study of rare human diseases...
  28. 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...
  29. ncbi Combined genetic profiles of components and regulators of the vitamin K-dependent gamma-carboxylation system affect individual sensitivity to warfarin
    Manuela Vecsler
    Molecular Genetics Unit, Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer 52621, Israel
    Thromb Haemost 95:205-11. 2006
    ..9 (1.9-18.4) for this genotype. Compound genetic profiles comprising VKORC1, CALU and CYP2C9 improve categorization of individual warfarin dose requirements in more than 25% of patients at steady-state anticoagulation...
  30. ncbi Binding of the factor IX gamma-carboxyglutamic acid domain to the vitamin K-dependent gamma-glutamyl carboxylase active site induces an allosteric effect that may ensure processive carboxylation and regulate the release of carboxylated product
    Pen Jen Lin
    Department of Biology, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    J Biol Chem 279:6560-6. 2004
    ..5) The increased dissociation rate after carboxylation contributes to the release of product...
  31. ncbi Four factor deficiency
    Angela Thomas
    Royal Hospital for Sick Children, Edinburgh, UK
    Blood Coagul Fibrinolysis 14:S55-7. 2003
    ..Expression studies are being completed so that this region can be definitively ascribed as a cis-acting element involved in gene regulation...
  32. ncbi Determination of disulfide bond assignment of human vitamin K-dependent gamma-glutamyl carboxylase by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
    Jian Ke Tie
    Department of Biology, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    J Biol Chem 278:45468-75. 2003
    ..Our results indicate that Cys-99 and Cys-450 form the only disulfide bond in carboxylase...
  33. doi The vitamin K cycle
    Johannes Oldenburg
    Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, D 53105 Bonn, Germany
    Vitam Horm 78:35-62. 2008
    ....
  34. doi Determinants of vitamin K status in humans
    Sarah L Booth
    Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA
    Vitam Horm 78:1-22. 2008
    ....
  35. ncbi Disulfide-dependent protein folding is linked to operation of the vitamin K cycle in the endoplasmic reticulum. A protein disulfide isomerase-VKORC1 redox enzyme complex appears to be responsible for vitamin K1 2,3-epoxide reduction
    Nadeem Wajih
    Department of Internal Medicine, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, USA
    J Biol Chem 282:2626-35. 2007
    ..We can conclude that the energy required for gamma-carboxylation of proteins is provided by dithiol-dependent oxidative protein folding in the ER and thus is linked to de novo protein synthesis...
  36. ncbi A quantum chemical study of the mechanism of action of Vitamin K carboxylase (VKC) III. Intermediates and transition states
    Charles H Davis
    Department of Biochemistry and Biophysics, UNC CH, Chapel Hill, 27599, United States
    J Mol Graph Model 26:409-14. 2007
    ..The results are consistent with the idea that the enzyme probably acts to facilitate the formation of the epoxide by reducing the energy required to deprotonate the hydroquinone form...
  37. ncbi Biochemical characterization of Drosophila gamma-glutamyl carboxylase and its role in fly development
    P K Bandyopadhyay
    Department of Biology, University of Utah, Salt Lake City, 84112, USA
    Insect Mol Biol 15:147-56. 2006
    ..Inactivation of Drosophila gamma-glutamyl carboxylase by non-sense mutations or insertional mutagenesis by P-element insertion have no apparent effects on growth and fertility under laboratory conditions...
  38. ncbi Polymorphisms in vitamin K-dependent gamma-carboxylation-related genes influence interindividual variability in plasma protein C and protein S activities in the general population
    Rina Kimura
    Research Institute, National Cardiovascular Center, Suita, Osaka, Japan
    Int J Hematol 84:387-97. 2006
    ..Thus, polymorphisms in genes involved in the vitamin K-dependent gamma-carboxylation reaction influence interindividual variation in the activities of protein C and protein S in the general population...
  39. ncbi [Gas-6 and protein S: vitamin K-dependent factors and ligands for the TAM tyrosine kinase receptors family]
    Omar Benzakour
    Institut de Physiologie et Biologie Cellulaires, France
    Med Sci (Paris) 23:826-33. 2007
    ....
  40. doi Vitamin K-dependent gamma-glutamylcarboxylation: an ancient posttranslational modification
    Pradip K Bandyopadhyay
    Department of Biology, University of Utah, 257 South 1400 East, Salt Lake City, Utah 84112, USA
    Vitam Horm 78:157-84. 2008
    ..melanogaster and C. textile...
  41. ncbi Crystal structures of biotin protein ligase from Pyrococcus horikoshii OT3 and its complexes: structural basis of biotin activation
    Bagautdin Bagautdinov
    Advanced Protein Crystallography Research Group, RIKEN Harima Institute at SPring 8, 1 1 1 Kouto, Mikazuki cho, Sayo gun, Hyogo 679 5148, Japan
    J Mol Biol 353:322-33. 2005
    ....
  42. ncbi Nutritional effects of gamma-glutamyl carboxylase gene polymorphism on the correlation between the vitamin K status and gamma-carboxylation of osteocalcin in young males
    Natsuko Sogabe
    Division of Nutrition, Department of Food and Nutrition, Japan Women s University, Tokyo, Japan
    J Nutr Sci Vitaminol (Tokyo) 53:419-25. 2007
    ..This is the first report to suggest the effects of the single nucleotide polymorphism R325Q in the GGCX gene on the correlation between the level of serum MK-7 and gamma-carboxylation of serum OC...
  43. ncbi Vitamin K epoxide reductase significantly improves carboxylation in a cell line overexpressing factor X
    Yan Mei Sun
    Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 3280, USA
    Blood 106:3811-5. 2005
    ..In addition to its mechanistic relevance, this observation has practical implications for overproducing recombinant vitamin K-dependent proteins for therapeutic use...
  44. ncbi 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
    ....
  45. ncbi 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
    ....
  46. ncbi 3-Methylcrotonyl-CoA carboxylase deficiency: mutation analysis in 28 probands, 9 symptomatic and 19 detected by newborn screening
    Maria Fernanda Dantas
    Division of Metabolism and Molecular Pediatrics, University Children s Hospital, Zurich, Switzerland
    Hum Mutat 26:164. 2005
    ..Our data demonstrate no clear correlation between genotype and phenotype suggesting that factors other than the genotype at the MCC loci have a major influence on the phenotype of MCC deficiency...
  47. ncbi Warfarin and the vitamin K-dependent gamma-carboxylation system
    Reidar Wallin
    Departments of Internal Medicine and Biochemistry, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA
    Trends Mol Med 10:299-302. 2004
    ..Identification of the 18-kDa protein has aided the understanding of the vitamin K-dependent gamma-carboxylation system at the molecular level...
  48. ncbi 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...
  49. pmc Characteristics and composition of the vitamin K-dependent gamma-glutamyl carboxylase-binding domain on osteocalcin
    Roger J T J Houben
    Department of Biochemistry and Cardiovascular Research Institute, Maastricht University, P O Box 616, 6200 MD Maastricht, The Netherlands
    Biochem J 364:323-8. 2002
    ....
  50. ncbi Clinical and biochemical findings on a child with multiple biotin-responsive carboxylase deficiencies
    K Narisawa
    J Inherit Metab Dis 5:67-8. 1982
  51. ncbi Chemical and catalytic mechanisms of carboxyl transfer reactions in biotin-dependent enzymes
    Paul V Attwood
    Department of Biochemistry, The University of Western Australia, Nedlands, WA 6907, Australia
    Acc Chem Res 35:113-20. 2002
    ....
  52. ncbi 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
    ....
  53. ncbi 1,25-Dihydroxyvitamin D3 promotes vitamin K2 metabolism in human osteoblasts
    N Miyake
    Department of Nutrition, Tokyo Metropolitan Institute of Gerontology, Japan
    Osteoporos Int 12:680-7. 2001
    ....
  54. ncbi Human biotin-containing subunit of 3-methylcrotonyl-CoA carboxylase gene (MCCA): cDNA sequence, genomic organization, localization to chromosomal band 3q27, and expression
    K Obata
    Department of Hygiene, Ehime University School of Medicine, Onsen gun, Ehime, 791 0295, Japan
    Genomics 72:145-52. 2001
    ....
  55. pmc The molecular basis of 3-methylcrotonylglycinuria, a disorder of leucine catabolism
    M E Gallardo
    Centro de Investigaciones Biologicas CSIC, Universidad Autonoma de Madrid, Madrid, Spain
    Am J Hum Genet 68:334-46. 2001
    ....
  56. ncbi On a potential global role for vitamin K-dependent gamma-carboxylation in animal systems. Evidence for a gamma-glutamyl carboxylase in Drosophila
    C S Walker
    Department of Biology, University of Utah, Salt Lake City, Utah 84112 0840, USA
    J Biol Chem 276:7769-74. 2001
    ..e. Conus), and Drosophila and the apparently strong homology between the three systems suggest that this is a highly conserved and widely distributed post-translational modification in biological systems...
  57. ncbi Novel mutation in the gamma-glutamyl carboxylase gene resulting in congenital combined deficiency of all vitamin K-dependent blood coagulation factors
    H M Spronk
    Department of Pediatrics, Sainte Therese Hospital, Beirut, Lebanon
    Blood 96:3650-2. 2000
    ..In 50 nonrelated normal subjects, the mutation was not found. This is the second time a missense mutation in the gamma-glutamyl carboxylase gene is described that has serious impact on normal hemostasis...
  58. pmc Osteocalcin binds tightly to the gamma-glutamylcarboxylase at a site distinct from that of the other known vitamin K-dependent proteins
    R J Houben
    Department of Biochemistry and Cardiovascular Research Institute, Maastricht University, P O Box 616, 6200 MD, Maastricht, The Netherlands
    Biochem J 341:265-9. 1999
    ..From our studies we conclude that descarboxy-osteocalcin must have an internal recognition sequence that binds to gamma-glutamylcarboxylase at a site different from the propeptide-recognition site...
  59. ncbi A conserved motif within the vitamin K-dependent carboxylase gene is widely distributed across animal phyla
    G S Begley
    Marine Biological Laboratory, Woods Hole, Massachusetts 02543, USA
    J Biol Chem 275:36245-9. 2000
    ..The vitamin K-dependent biosynthesis of gamma-carboxyglutamic acid appears to be a highly conserved function in the animal kingdom...
  60. ncbi Process of carboxylation of glutamic acid residues in the gla domain of human des-gamma-carboxyprothrombin
    S Uehara
    Department of Gastroenterology, Tonan Hospital, N1, W6, Chuoku, Sapporo, Japan
    Clin Chim Acta 289:33-44. 1999
    ..The process of Glu carboxylation seemed to proceed three-dimensionally from inside to outside the molecule...
  61. ncbi The putative vitamin K-dependent gamma-glutamyl carboxylase internal propeptide appears to be the propeptide binding site
    Pen Jen Lin
    Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 3280, USA
    J Biol Chem 277:28584-91. 2002
    ..These results agree with our previous observations, indicating that residues in this region are involved in propeptide binding...
  62. ncbi Identification of a Drosophila vitamin K-dependent gamma-glutamyl carboxylase
    T Li
    Department of Biology, Center for Thrombosis and Homeostasis, University of North Carolina, Chapel Hill, North Carolina 27599 3280, USA
    J Biol Chem 275:18291-6. 2000
    ..We found the mRNA for Drosophila gamma-glutamyl carboxylase in virtually every embryonic and adult stage that we investigated, with the highest concentration evident in the adult head...
  63. pmc Characterization of a bifunctional archaeal acyl coenzyme A carboxylase
    Songkran Chuakrut
    Laboratory of Applied Microbiology, Department of Biotechnology, The University of Tokyo, Yayoi 1 1 1, Bunkyo ku, Tokyo 113 8567, Japan
    J Bacteriol 185:938-47. 2003
    ..The acyl-CoA-binding site and the carboxybiotin-binding site were found in the carboxyltransferase subunit...
  64. ncbi Vitamin K 2,3-epoxide reductase and the vitamin K-dependent gamma-carboxylation system
    Reidar Wallin
    Department of Internal Medicine, Section on Rheumatology, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA
    Thromb Res 108:221-6. 2002
    ..This finding puts VKOR in a central position to regulate biosynthesis of biologically active vitamin K-dependent proteins...
  65. ncbi Expression and characterization of recombinant vitamin K-dependent gamma-glutamyl carboxylase from an invertebrate, Conus textile
    Eva Czerwiec
    Marine Biological Laboratory, Woods Hole, MA, USA
    Eur J Biochem 269:6162-72. 2002
    ....
  66. ncbi A missense mutation in gamma-glutamyl carboxylase gene causes combined deficiency of all vitamin K-dependent blood coagulation factors
    B Brenner
    Thrombosis and Hemostasis Unit, Institute of Hematology, Rambam Medical Center, and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel
    Blood 92:4554-9. 1998
    ..The mutated carboxylase protein expressed in Drosophila cells was stable but demonstrated threefold reduced activity compared with WT carboxylase, confirming that the L394R mutation results in a defective carboxylase...
  67. ncbi High-resolution SNP and haplotype maps of the human gamma-glutamyl carboxylase gene (GGCX) and association study between polymorphisms in GGCX and the warfarin maintenance dose requirement of the Japanese population
    Pei Chieng Cha
    Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4 6 1 Shirokanedai, Minato ku, Tokyo 108 8639, Japan
    J Hum Genet 52:856-64. 2007
    ..We found no significant association between the polymorphisms in GGCX and the dose requirement...
  68. doi [Vitamin K function mediated by activation of steroid and xenobiotic receptor]
    Kotaro Azuma
    Department of Geriatric Medicine, The Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
    Clin Calcium 19:1770-8. 2009
    ..It has been also suggested that vitamin K could prevent or treat the hepatocellular carcinoma (HCC) in some clinical studies. SXR may also contribute to the vitamin K-dependent reduction of HCC...
  69. ncbi Gamma-glutamyl carboxylase (GGCX) tagSNPs have limited utility for predicting warfarin maintenance dose
    M J Rieder
    Department of Genome Sciences, Epidemiology, and Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA
    J Thromb Haemost 5:2227-34. 2007
    ..Gamma-glutamyl carboxylase (GGCX), in its role as a key component of the vitamin K cycle, is a potential candidate gene associated with warfarin treatment...
  70. ncbi Quantum chemical study of the mechanism of action of vitamin K carboxylase (VKC). IV. Intermediates and transition states
    Charles H Davis
    Department of Biochemistry, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    J Phys Chem A 111:7257-61. 2007
    ..We relate these computations to the entire vitamin K cycle in the blood coagulation cascade, which is essential for viability of vertebrates...
  71. pmc Pseudoxanthoma elasticum: molecular genetics and putative pathomechanisms
    Jouni Uitto
    Department of Dermatology and Cutaneous Biology, Jefferson Medical College and Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA
    J Invest Dermatol 130:661-70. 2010
    ..Understanding of the pathomechanistic details of PXE provides a basis for the development of targeted molecular therapies for this currently intractable disease...
  72. doi Genotype polymorphisms of GGCX, NQO1, and VKORC1 genes associated with risk susceptibility in patients with large-artery atherosclerotic stroke
    Hann Yeh Shyu
    Neurology Section, Internal Medicine Department, Armed Forces Taoyuan General Hospital, Taoyuan, Taiwan
    Clin Chim Acta 411:840-5. 2010
    ..We evaluated the role of these genotype polymorphisms in patients with large-artery atherosclerotic stroke...
  73. doi Activity and expression of vitamin K-dependent gamma-glutamyl carboxylase in patients with calcium oxalate urolithiasis
    Tao Wang
    Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
    Urol Int 85:94-9. 2010
    ..To evaluate the correlation between vitamin K-dependent gamma-glutamyl carboxylase (GGCX) and the formation of calcium oxalate urolithiasis (COU)...
  74. pmc Combined genomic and proteomic approaches identify gene clusters involved in anaerobic 2-methylnaphthalene degradation in the sulfate-reducing enrichment culture N47
    Drazenka Selesi
    Institute of Groundwater Ecology, Helmholtz Zentrum Munchen German Research Center for Environmental Health, Ingolstadter Landstrasse 1, D 85764 Neuherberg, Germany
    J Bacteriol 192:295-306. 2010
    ..The present work provides the first insight into the genetic basis of anaerobic 2-methylnaphthalene metabolism and delivers implications for understanding contaminant degradation...
  75. ncbi [Molecular mechanism of vitamin K and its regulators in bone metabolism]
    Tohru Tsukui
    Saitama Medical University, Research Center for Genomic Medicine
    Clin Calcium 17:1685-91. 2007
    ..The other pathway is a novel one, that mediates the transcriptional regulation of the target genes by SXR, steroid and xenobiotic receptor. Both mechanisms of VK are involved in modulation of extracellular matrix proteins in the bone...
  76. doi Gamma-glutamyl carboxylase R325Q polymorphism on the response of acenocoumarol
    Rocio Gonzalez-Conejero
    Thromb Res 122:429-31. 2008
  77. doi AMP-activated protein kinase agonist dose dependently improves function and reduces apoptosis in glucotoxic beta-cells without changing triglyceride levels
    Hanna K Nyblom
    Department of Medical Cell Biology, Uppsala University, Box 571, SE 751 23 Uppsala, Sweden
    J Mol Endocrinol 41:187-94. 2008
    ..In conclusion, AICAR dose dependently improves beta-cell function and reduces apoptosis in beta-cells exposed to prolonged hyperglycaemia without changing TG levels...
  78. pmc Isolation of cDNA clones coding for the alpha and beta chains of human propionyl-CoA carboxylase: chromosomal assignments and DNA polymorphisms associated with PCCA and PCCB genes
    A M Lamhonwah
    Proc Natl Acad Sci U S A 83:4864-8. 1986
    ..Restriction fragment length polymorphisms were identified, at both PCCA and PCCB, that should prove useful to individual families at risk for propionic acidemia...
  79. doi Leaf succulence determines the interplay between carboxylase systems and light use during Crassulacean acid metabolism in Kalanchöe species
    Howard Griffiths
    Physiological Ecology Group, Department of Plant Sciences, Downing Street, University of Cambridge, Downing Street, Cambridge CB2 3EA, UK
    J Exp Bot 59:1851-61. 2008
    ..daigremontiana. Leaf morphology therefore seems to alter the expression of and dependence on CAM, but also the extent of co-regulation of carboxylase networks and light use capacity...
  80. pmc Propionicacidemia: absence of alpha-chain mRNA in fibroblasts from patients of the pccA complementation group
    A M Lamhonwah
    Research Institute, Hospital for Sick Children, Toronto, Canada
    Am J Hum Genet 41:1124-31. 1987
    ....
  81. pmc Mutations in the GGCX and ABCC6 genes in a family with pseudoxanthoma elasticum-like phenotypes
    Qiaoli Li
    Department of Dermatology and Cutaneous Biology, Jefferson Medical College, Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    J Invest Dermatol 129:553-63. 2009
    ..These findings expand the molecular basis of PXE-like phenotypes, and suggest a role for multiple genetic factors in pathologic tissue mineralization in general...
  82. pmc Molecular cloning and characterization of the cDNA coding for the biotin-containing subunit of 3-methylcrotonoyl-CoA carboxylase: identification of the biotin carboxylase and biotin-carrier domains
    J Song
    Department of Biochemistry and Biophysics, Iowa State University, Ames 50011
    Proc Natl Acad Sci U S A 91:5779-83. 1994
    ..These domains are arranged serially on the polypeptide, with the biotin carboxylase domain at the amino terminus and the biotin-carboxyl carrier domain at the carboxyl terminus...
  83. pmc Sexual differentiation of the zebra finch song system: potential roles for sex chromosome genes
    Michelle L Tomaszycki
    Department of Psychology and Program in Neuroscience, Michigan State University, East Lansing, MI, USA
    BMC Neurosci 10:24. 2009
    ..The present study examined the potential role for sex-biased gene expression during development of sexually dimorphic singing behavior and associated song nuclei in juvenile zebra finches...
  84. pmc In vitro and in vivo functional characterization of bovine vitamin K-dependent gamma-carboxylase expressed in Chinese hamster ovary cells
    A Rehemtulla
    Genetics Institute, Cambridge, MA 02140
    Proc Natl Acad Sci U S A 90:4611-5. 1993
    ..These results demonstrate that the ability of CHO cells to modify glutamic acid residues to gamma-carboxyglutamic acid in secreted factor IX is not limited by the expression of the vitamin K-dependent gamma-carboxylase alone...
  85. doi Vitamin K-dependent coagulation factors deficiency
    Benjamin Brenner
    Thrombosis and Hemostasis Unit, Institute of Hematology, Rambam Medical Center, and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel
    Semin Thromb Hemost 35:439-46. 2009
    ..Laboratory assays used for diagnosis will be discussed, and treatment for various clinical settings will be recommended...
  86. pmc Cryptic exon activation by disruption of exon splice enhancer: novel mechanism causing 3-methylcrotonyl-CoA carboxylase deficiency
    Martin Stucki
    Division of Metabolism, University Children s Hospital, 8032 Zurich, Switzerland
    J Biol Chem 284:28953-7. 2009
    ..To our knowledge, this is the first demonstration of a point mutation disrupting an exon splice enhancer that causes exon skipping along with utilization of a cryptic exon...
  87. doi The carboxylation efficiency of the vitamin K-dependent clotting factors: studies with factor IX
    M Blostein
    SMDB Jewish General Hospital, Montreal, QC, Canada
    Haemophilia 14:1063-8. 2008
    ..These results demonstrate that the nature of the propeptide, per se is not the sole determinant of optimal carboxylation of FIX in our expression system in HEK 293 cells...
  88. pmc AccD6, a member of the Fas II locus, is a functional carboxyltransferase subunit of the acyl-coenzyme A carboxylase in Mycobacterium tuberculosis
    Jaiyanth Daniel
    Burnett College of Biomedical Sciences, University of Central Florida, BMS 136, 4000 Central Florida Blvd, Orlando, FL 32816 2364, USA
    J Bacteriol 189:911-7. 2007
    ..Our results suggest that the beta6 subunit could play an important role in mycolic acid biosynthesis by providing malonyl-CoA to the FAS II complex...
  89. ncbi Molecular mechanism of dominant expression in 3-methylcrotonyl-CoA carboxylase deficiency
    M R Baumgartner
    Division of Metabolism and Molecular Pediatrics, University Children s Hospital Zurich, Switzerland
    J Inherit Metab Dis 28:301-9. 2005
    ..Evidence is presented that MCCA-R385S is a dominant negative allele leading to biochemical abnormalities and clinical symptoms in heterozygous individuals and that it is responsive to pharmacological doses of biotin in vivo...
  90. ncbi Biotin supplementation increases expression of genes encoding interferon-gamma, interleukin-1beta, and 3-methylcrotonyl-CoA carboxylase, and decreases expression of the gene encoding interleukin-4 in human peripheral blood mononuclear cells
    Silke Wiedmann
    Department of Nutritional Science and Dietetics, University of Nebraska at Lincoln, 68583, USA
    J Nutr 133:716-9. 2003
    ..These data suggest that biotin supplementation affects gene expression in human immune cells. Effects of biotin on gene expression are likely to modulate the response of immune cells to antigens...
  91. ncbi Characteristics of recombinant W501S mutated human gamma-glutamyl carboxylase
    B A M Soute
    Cardiovascular Research Institute Maastricht, Department of Biochemistry, University of Maastricht, Maastricht, The Netherlands
    J Thromb Haemost 2:597-604. 2004
    ....
  92. ncbi Leukodystrophy and CSF purine abnormalities associated with isolated 3-methylcrotonyl-CoA carboxylase deficiency
    Raquel Dodelson de Kremer
    Centro de Estudio de las Metabolopatias Congenitas, Universidad Nacional de Cordoba, Hospital de Ninos, Cordoba, Argentina
    Metab Brain Dis 17:13-8. 2002
    ..This case extends the phenotype of isolated MCC deficiency in infancy and suggests this entity should be considered to be one of the possible causes of "metabolic leukodystrophies."..
  93. ncbi Propionic acidemia: analysis of mutant propionyl-CoA carboxylase enzymes expressed in Escherichia coli
    Maja Chloupkova
    Department of Pediatrics, University of Colorado School of Medicine, Denver, Colorado, USA
    Hum Mutat 19:629-40. 2002
    ....
  94. ncbi Paracetamol (acetaminophen) warfarin interaction: NAPQI, the toxic metabolite of paracetamol, is an inhibitor of enzymes in the vitamin K cycle
    Henk H Thijssen
    Department of Pharmacology, Cardiovascular Research Institute Maastricht CARIM, University of Maastricht, P O Box 616, 6200 MD Maastricht, The Netherlands
    Thromb Haemost 92:797-802. 2004
    ..We conclude that, the potentiation of the oral anticoagulant effect by paracetamol is likely to result from NAPQI-induced inhibition of enzymes of the vitamin K cycle, particularly VKD-carb...
  95. ncbi Diaminobiotin and desthiobiotin have biotin-like activities in Jurkat cells
    Rocio Rodriguez-Melendez
    Department of Nutritional Science and Dietetics, University of Nebraska at Lincoln, Lincoln, NE, USA
    J Nutr 133:1259-64. 2003
    ..It is not known whether naturally occurring biotin metabolites also have biotin-like activities...
  96. ncbi Mutation spectrum of the PCCA and PCCB genes in Japanese patients with propionic acidemia
    Xue Yang
    Department of Medical Genetics, Tohoku University School of Medicine, 1 1 Seiryo machi, Aoba ku, Sendai 980 8574, Japan
    Mol Genet Metab 81:335-42. 2004
    ..7, and 13.3%, respectively. In conclusion, a limited number of mutations are predominant in both PCCA and PCCB genes among Japanese patients with propionic acidemia...
  97. ncbi The abundance and function of biotin-dependent enzymes are reduced in rats chronically administered carbamazepine
    Sara C Rathman
    Center for Nutritional Sciences, Food Science and Human Nutrition Department, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL 32611, USA
    J Nutr 132:3405-10. 2002
    ....
  98. ncbi External surface display of proteins linked to DNA-binding domains
    D P McGregor
    Skeletal Metabolism Research Unit, Rowett Research Institute, Greenburn Road, Bucksburn, Aberdeen, AB21 9SB, Scotland
    Anal Biochem 294:108-17. 2001
    ..This display system may complement currently available bacterial selection techniques...
  99. ncbi Partial response to biotin therapy in a patient with holocarboxylase synthetase deficiency: clinical, biochemical, and molecular genetic aspects
    R Santer
    Department of General Pediatrics, University Children s Hospital Kiel, Germany
    Mol Genet Metab 79:160-6. 2003
    ..This case illustrates mechanisms involved in the genotype-phenotype correlation that unequivocally exists in HCS deficiency...
  100. ncbi Pharmacogenetics of target genes across the warfarin pharmacological pathway
    Suman Lal
    National Cancer Centre, Laboratory of Clinical Pharmacology, Division of Medical Sciences, Singapore, Singapore
    Clin Pharmacokinet 45:1189-200. 2006
    ..Understanding the causal relationship of these polygenic influences on warfarin dose requirements in patients of different ethnicity may be vital in reducing inter-patient variability and optimising anticoagulant therapy...
  101. ncbi New splicing mutations in propionic acidemia
    Lourdes R Desviat
    Centro de Biologia Molecular Severo Ochoa CSIC UAM, Universidad Autonoma de Madrid, Cantoblanco, 28049 Madrid, Spain
    J Hum Genet 51:992-7. 2006
    ..The results highlight the necessity to perform transcript analysis in addition to genomic DNA sequencing to characterize the effect of splicing mutations and add relevant information on the genetic epidemiology of the disease...

Research Grants107 found, 100 shown here

  1. VITAMIN K, METABOLISM AND FUNCTION
    Reidar Wallin; Fiscal Year: 2001
    ..The experiments should also contribute to the exciting, rapidly expanding area of research on extra-hepatic vitamin K-dependent proteins. ..
  2. Vitamin K, Bone, and Arterial Calcification
    Reidar Wallin; Fiscal Year: 2006
    ..The proposed work will provide basic knowledge of BMP-2 growth factor mediated calcification as it is linked to the function of a fat-soluble vitamin (vitamin K) and biosynthesis of vitamin K-dependent proteins. ..
  3. Structure-Function Analysis of the Gamma-Carboxylase
    KATHLEEN BERKNER; Fiscal Year: 2003
    ....
  4. LUNG TRANSCRIPTION FACTOR, LKLF-1
    Jerry Lingrel; Fiscal Year: 2000
    ....
  5. 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. ..
  6. Molecular Genetics of Familial Tumoral Calcinosis
    Jouni Uitto; Fiscal Year: 2009
    ..abstract_text> ..
  7. HMGB1/2 and Cellular Response to Fraudulent Nucleosides
    Evgeny Krynetskiy; Fiscal Year: 2007
    ..abstract_text> ..
  8. COLLAGEN BIOSYNTHESIS OF CULTURED FIBROBLASTS
    Jouni Uitto; Fiscal Year: 2006
    ....
  9. Biotin Status in Pregnancy
    Donald M Mock; Fiscal Year: 2010
    ..Given the expense of such trials, the smaller study proposed here is an essential prerequisite in a line of research with substantial healthcare implications. ..
  10. 12th International Symposium on Basement Membranes
    Jouni Uitto; Fiscal Year: 2005
    ..In that sense, the meeting will meet some of the goals of the National Institutes of Health Roadmap Initiative. ..
  11. Vitamin K Oxidoreductase: function and physiology
    KATHLEEN LUCILE BERKNER; Fiscal Year: 2010
    ....
  12. BIOCHEMISTRY AND MORPHOLOGY OF CONNECTIVE TISSUE
    Jouni Uitto; Fiscal Year: 1993
    ..Elucidation of normal biochemistry and molecular biology of elastin provides a basis to explore elastin aberrations in clinical situations in the future...
  13. BIOCHEMISTRY AND MORPHOLOGY OF CONNECTIVE TISSUE
    Jouni Uitto; Fiscal Year: 2009
    ..Such information is critical for development of translational strategies to counteract this devastating multi-system disease. ..
  14. COLLAGEN BIOSYNTHESIS BY CULTURED FIBROBLASTS
    Jouni Uitto; Fiscal Year: 1993
    ..The results will also provide us with knowledge highly useful for the development of rationale treatment modalities for these conditions...
  15. NA,K-ATPase: Role of Alpha Isoforms
    Jerry B Lingrel; Fiscal Year: 2010
    ..In the present proposal we will investigate this phenomenon and define the mechanism by which the ouabain binding site of Na,K-ATPase regulates maternal blood pressure. ..
  16. Molecular Genetics of the Cutaneous BMZ in EB
    JOUNI contact UITTO; Fiscal Year: 2010
    ..Results of our study will establish minimal targets that have to be reached to correct pathological changes in skin caused by mutations in procollagen VII. Thus, the relevance of our proposed research for public health is high. ..
  17. FUNCTIONAL STUDIES OF THE NA,K-ATPASE
    Jerry Lingrel; Fiscal Year: 2009
    ..These matings will provide animals where the alpha2 isoform is missing only in heart or smooth muscle and this will allow us to study the specific role of this isoform in cardiovascular function. ..
  18. Model Systems for PXE
    Jouni Uitto; Fiscal Year: 2010
    ..The results are expected to provide novel approaches to ameliorate, and perhaps cure, PXE and other related, currently intractable, mineralization disorders. ..
  19. Gene delivery to striated muscle by systemic AAV vectors
    Dwight D Koeberl; Fiscal Year: 2010
    ..Efficacious muscle-targeted gene therapy in GSD-II will have implications for gene therapy in other muscular dystrophies and myopathies. ..
  20. Mechanisms for immune tolerance in Pompe Disease
    Dwight D Koeberl; Fiscal Year: 2010
    ..These comparisons will guide preclinical experiments to further immunomodulatory gene therapy in Pompe disease and other lysosomal storage disorders. ..
  21. Diet treatment of Galactosemic Infants: A Pilot Study
    Can Ficicioglu; Fiscal Year: 2007
    ..Evidence from this study may have a future impact on how newborn galactosemics are treated with a potential for moderating long-term complications. ..
  22. Gene delivery to striated muscle by systemic AAV vectors
    Dwight Koeberl; Fiscal Year: 2007
    ..Efficacious muscle-targeted gene therapy in GSD-II will have implications for gene therapy in other muscular dystrophies and myopathies. ..
  23. Aspects of Biotin Nutrition
    Donald Mock; Fiscal Year: 2007
    ..Specific Aim #4: In healthy adult volunteers, we will experimentallyinduce marginal biotin deficiencyusing a modified outpatient design and assess the utility of promising new indicators of biotin status. ..
  24. DYSGENIC KIDNEY LETHAL MUTANT MICE
    Jerry Lingrel; Fiscal Year: 2003
    ..These studies will lead to an understanding of how the functions of new genes affect kidney development and provide an insight into the process of nephrogenesis. ..
  25. CHARACTERIZATION OF NA,K-ATPASE AND ITS GENES
    Jerry Lingrel; Fiscal Year: 1993
    ....
  26. Structure-Function Analysis of the Gamma-Carboxylase
    KATHLEEN BERKNER; Fiscal Year: 2006
    ..abstract_text> ..
  27. The Role of the KLF2 in Vascular Endothelial Cells
    Jerry Lingrel; Fiscal Year: 2007
    ..Importantly, they will serve as a prerequisite for further investigation of KLF2 as a vaso-protective therapeutic target. ..
  28. Studies of the Lung Kruppel-Like Transcription Factor
    Jerry Lingrel; Fiscal Year: 2004
    ..We will use gene microarray analysis of cells with and without the LKLF gene and develop conditional expression of LKLF to define downstream target genes in tissues such as lung, macrophages and T-lymphocytes. ..
  29. INDICES OF BIOTIN NUTRITION
    Donald Mock; Fiscal Year: 2001
    ..4) Whether biotin deficiency of similar severity to that observed either early or late in human gestation causes increased rates of fetal malformation in the mouse. 5) The enzyme(s) responsible for biotin beta-oxidation. ..
  30. 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. ..
  31. NA+ K+ ATPASE STRUCTURE/FUNCTION STUDIES
    Jerry Lingrel; Fiscal Year: 1999
    ..Finally, we will study the cardiac glycoside binding characteristics of human Na,K-ATPase carrying the alpha1, alpha2 and alpha3 isoforms. ..
  32. CHARACTERIZATION OF THE NA+,K+ ATPASE AND ITS GENES
    Jerry Lingrel; Fiscal Year: 1990
    ..This study should determine whether the basis for resistance to this drug resides in the Alpha subunit and define the differences between the mutant and wild type genes...
  33. MURINE KNOCKOUT MODEL OF 4-HYDROXYBUTYRIC ACIDURIA
    K Michael Gibson; Fiscal Year: 2007
    ....
  34. Gene delivery to striated muscle by systemic AAV vectors
    Dwight Koeberl; Fiscal Year: 2009
    ..Efficacious muscle-targeted gene therapy in GSD-II will have implications for gene therapy in other muscular dystrophies and myopathies. ..