THOMAS ROCHE

Summary

Affiliation: Kansas State University
Country: USA

Publications

  1. ncbi request reprint Essential roles of lipoyl domains in the activated function and control of pyruvate dehydrogenase kinases and phosphatase isoform 1
    Thomas E Roche
    Department of Biochemistry, Kansas State University, Manhattan, Kansas 66506, USA
    Eur J Biochem 270:1050-6. 2003
  2. ncbi request reprint Pyruvate dehydrogenase kinase regulatory mechanisms and inhibition in treating diabetes, heart ischemia, and cancer
    T E Roche
    Department of Biochemistry, Kansas State University, Chalmers Hall, Manhattan, KS 66506, USA
    Cell Mol Life Sci 64:830-49. 2007
  3. ncbi request reprint Pyruvate dehydrogenase kinase isoform 2 activity stimulated by speeding up the rate of dissociation of ADP
    Haiying Bao
    Department of Biochemistry, Kansas State University, Manhattan, Kansas 66506, USA
    Biochemistry 43:13442-51. 2004
  4. ncbi request reprint Formation of a complex of the catalytic subunit of pyruvate dehydrogenase phosphatase isoform 1 (PDP1c) and the L2 domain forms a Ca2+ binding site and captures PDP1c as a monomer
    Ali Turkan
    Department of Biochemistry, Kansas State University, Manhattan, Kansas 66506, USA
    Biochemistry 43:15073-85. 2004
  5. ncbi request reprint Pyruvate dehydrogenase kinase isoform 2 activity limited and further inhibited by slowing down the rate of dissociation of ADP
    Haiying Bao
    Department of Biochemistry, Kansas State University, Manhattan, Kansas 66506, USA
    Biochemistry 43:13432-41. 2004
  6. ncbi request reprint Facilitated interaction between the pyruvate dehydrogenase kinase isoform 2 and the dihydrolipoyl acetyltransferase
    Yasuaki Hiromasa
    Department of Biochemistry, Kansas State University, Manhattan, Kansas 66506, USA
    J Biol Chem 278:33681-93. 2003
  7. ncbi request reprint Ligand-induced effects on pyruvate dehydrogenase kinase isoform 2
    Yasuaki Hiromasa
    Department of Biochemistry, Kansas State University, Manhattan, Kansas 66506, USA
    J Biol Chem 281:12568-79. 2006
  8. ncbi request reprint Structural requirements within the lipoyl domain for the Ca2+-dependent binding and activation of pyruvate dehydrogenase phosphatase isoform 1 or its catalytic subunit
    Ali Turkan
    Department of Biochemistry, Kansas State University, Manhattan, Kansas 66506, USA
    J Biol Chem 277:14976-85. 2002
  9. doi request reprint Specific ion influences on self-association of pyruvate dehydrogenase kinase isoform 2 (PDHK2), binding of PDHK2 to the L2 lipoyl domain, and effects of the lipoyl group-binding site inhibitor, Nov3r
    Yasuaki Hiromasa
    Department of Biochemistry, Kansas State University, Manhattan, Kansas 66506, USA
    Biochemistry 47:2312-24. 2008
  10. ncbi request reprint Organization of the cores of the mammalian pyruvate dehydrogenase complex formed by E2 and E2 plus the E3-binding protein and their capacities to bind the E1 and E3 components
    Yasuaki Hiromasa
    Department of Biochemistry, Kansas State University, Manhattan, Kansas 66506, USA
    J Biol Chem 279:6921-33. 2004

Research Grants

  1. REGULATION OF MAMMALIAN PYRUVATE DEHYDROGENASE
    THOMAS ROCHE; Fiscal Year: 2000
  2. REGULATION OF MAMMALIAN PYRUVATE DEHYDROGENASE
    THOMAS ROCHE; Fiscal Year: 1990
  3. REGULATION OF MAMMALIAN PYRUVATE DEHYDROGENASE
    THOMAS ROCHE; Fiscal Year: 2004

Collaborators

  • Yasuaki Hiromasa
  • Haiying Bao
  • Ali Turkan
  • Xiaohua Yan
  • Shane A Kasten
  • Xuekui Yu
  • Thorsten R Knoechel
  • Sylvaine F A Bruggraber
  • Hua Tsen
  • James K Stoops
  • Z Hong Zhou
  • Colin M Robinson
  • Wendy Taylor
  • Alec D Tucker
  • David G Brown
  • Liangyan Hu
  • Peter J Bungay
  • Chris Phillips
  • Yoichi Aso
  • Tetsuro Fujisawa
  • Katsushi Amano
  • Chao Quan
  • M Eric Gershwin
  • Aftab A Ansari
  • Velimer Luketic
  • Michael H Nantz
  • Judy Van de Water
  • Mark J Kurth
  • Patrick S C Leung
  • Gordon D Benson
  • Ross L Coppel
  • Xiaoming Gong
  • Tao Peng

Detail Information

Publications14

  1. ncbi request reprint Essential roles of lipoyl domains in the activated function and control of pyruvate dehydrogenase kinases and phosphatase isoform 1
    Thomas E Roche
    Department of Biochemistry, Kansas State University, Manhattan, Kansas 66506, USA
    Eur J Biochem 270:1050-6. 2003
    ....
  2. ncbi request reprint Pyruvate dehydrogenase kinase regulatory mechanisms and inhibition in treating diabetes, heart ischemia, and cancer
    T E Roche
    Department of Biochemistry, Kansas State University, Chalmers Hall, Manhattan, KS 66506, USA
    Cell Mol Life Sci 64:830-49. 2007
    ..PDC activation also triggers apoptosis in cancer cells that selectively convert glucose to lactate...
  3. ncbi request reprint Pyruvate dehydrogenase kinase isoform 2 activity stimulated by speeding up the rate of dissociation of ADP
    Haiying Bao
    Department of Biochemistry, Kansas State University, Manhattan, Kansas 66506, USA
    Biochemistry 43:13442-51. 2004
    ..We suggest that passing even limited reducing equivalents among lipoyl groups maintains E2 lipoyl domains in a conformation that aids kinase function...
  4. ncbi request reprint Formation of a complex of the catalytic subunit of pyruvate dehydrogenase phosphatase isoform 1 (PDP1c) and the L2 domain forms a Ca2+ binding site and captures PDP1c as a monomer
    Ali Turkan
    Department of Biochemistry, Kansas State University, Manhattan, Kansas 66506, USA
    Biochemistry 43:15073-85. 2004
    ..Therefore, both proteins are required for formation of a complex with tightly held Ca(2+), and complex formation hinders the tendency of PDP1c to form a dimer...
  5. ncbi request reprint Pyruvate dehydrogenase kinase isoform 2 activity limited and further inhibited by slowing down the rate of dissociation of ADP
    Haiying Bao
    Department of Biochemistry, Kansas State University, Manhattan, Kansas 66506, USA
    Biochemistry 43:13432-41. 2004
    ..ADP or ATP].pyruvate complexes form, and that PDK2.ATP.pyruvate.E1 reacts with PDK2.ADP.pyruvate accumulating...
  6. ncbi request reprint Facilitated interaction between the pyruvate dehydrogenase kinase isoform 2 and the dihydrolipoyl acetyltransferase
    Yasuaki Hiromasa
    Department of Biochemistry, Kansas State University, Manhattan, Kansas 66506, USA
    J Biol Chem 278:33681-93. 2003
    ....
  7. ncbi request reprint Ligand-induced effects on pyruvate dehydrogenase kinase isoform 2
    Yasuaki Hiromasa
    Department of Biochemistry, Kansas State University, Manhattan, Kansas 66506, USA
    J Biol Chem 281:12568-79. 2006
    ..Ligand-induced changes that interfere with PDHK2 binding to GST-L2(red) may involve release of an interdomain cross arm between PDHK2 subunits in which Trp-383 plays a critical anchoring role...
  8. ncbi request reprint Structural requirements within the lipoyl domain for the Ca2+-dependent binding and activation of pyruvate dehydrogenase phosphatase isoform 1 or its catalytic subunit
    Ali Turkan
    Department of Biochemistry, Kansas State University, Manhattan, Kansas 66506, USA
    J Biol Chem 277:14976-85. 2002
    ..Our results indicate hydrophobic binding via the extended aliphatic structure of the lipoyl group and required adjacent L2 structure anchor PDP1 by acting in concert with an acidic cluster at the other end of the domain...
  9. doi request reprint Specific ion influences on self-association of pyruvate dehydrogenase kinase isoform 2 (PDHK2), binding of PDHK2 to the L2 lipoyl domain, and effects of the lipoyl group-binding site inhibitor, Nov3r
    Yasuaki Hiromasa
    Department of Biochemistry, Kansas State University, Manhattan, Kansas 66506, USA
    Biochemistry 47:2312-24. 2008
    ..Pi is suggested to facilitate transmission within PDHK2 of the stimulatory signal of acetylation from the distal lipoyl-group binding site to the active site...
  10. ncbi request reprint Organization of the cores of the mammalian pyruvate dehydrogenase complex formed by E2 and E2 plus the E3-binding protein and their capacities to bind the E1 and E3 components
    Yasuaki Hiromasa
    Department of Biochemistry, Kansas State University, Manhattan, Kansas 66506, USA
    J Biol Chem 279:6921-33. 2004
    ..Twelve E3 dimers were bound per E248.E3BP12 mass, which is consistent with this model...
  11. doi request reprint Critical role of specific ions for ligand-induced changes regulating pyruvate dehydrogenase kinase isoform 2
    Yasuaki Hiromasa
    Department of Biochemistry, Kansas State University, Manhattan, Kansas 66506, USA
    Biochemistry 47:2298-311. 2008
    ..Pi effects were minimal when NH4+ replaced K+. We have quantified coupled binding of K+ with ATP and ADP and elucidated how linked K+ and Pi binding are required for the potent inhibition of PDHK2 by ADP and pyruvate...
  12. ncbi request reprint Regulatory roles of the N-terminal domain based on crystal structures of human pyruvate dehydrogenase kinase 2 containing physiological and synthetic ligands
    Thorsten R Knoechel
    PGRD Sandwich, Pfizer Ltd, Sandwich, Kent CT139NJ, United Kingdom
    Biochemistry 45:402-15. 2006
    ..The structures we describe provide insights that can be used for structure-based design of PDHK inhibitors...
  13. ncbi request reprint Autoreactivity to lipoate and a conjugated form of lipoate in primary biliary cirrhosis
    Sylvaine F A Bruggraber
    Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis Medical School, 95616, USA
    Gastroenterology 125:1705-13. 2003
    ..The immunodominant autoantigen in primary biliary cirrhosis (PBC), E2 components of pyruvate dehydrogenase complexes (PDC-E2), has a lipoate molecule bonded to the domain to which autoantibodies are directed...
  14. doi request reprint Structures of the human pyruvate dehydrogenase complex cores: a highly conserved catalytic center with flexible N-terminal domains
    Xuekui Yu
    Department of Pathology and Laboratory Medicine, The University of Texas Medical School at Houston, Houston, TX 77030, USA
    Structure 16:104-14. 2008
    ....

Research Grants15

  1. REGULATION OF MAMMALIAN PYRUVATE DEHYDROGENASE
    THOMAS ROCHE; Fiscal Year: 2000
    ..Aberrant PDC operation is associated with diabetes and obesity. Inborn errors in components cause severe defects. Primary biliary cirrhosis is an autoimmune disease with antibodies to E2 and other PDC subunits. ..
  2. REGULATION OF MAMMALIAN PYRUVATE DEHYDROGENASE
    THOMAS ROCHE; Fiscal Year: 1990
    ....
  3. REGULATION OF MAMMALIAN PYRUVATE DEHYDROGENASE
    THOMAS ROCHE; Fiscal Year: 2004
    ..The long term objective is to understand the tissue-specific control of PDC and to delineate the unique properties of kinase isoforms overexpressed in diabetes which inactivates PDC thereby minimize glucose use. ..