Research TopicsSpecies | THOMAS ROCHESummaryAffiliation: Kansas State University Country: USA Publications
Research Grants
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Detail Information
Publications
Essential roles of lipoyl domains in the activated function and control of pyruvate dehydrogenase kinases and phosphatase isoform 1Thomas E Roche
Department of Biochemistry, Kansas State University, Manhattan, Kansas 66506, USA
Eur J Biochem 270:1050-6. 2003....
Pyruvate dehydrogenase kinase regulatory mechanisms and inhibition in treating diabetes, heart ischemia, and cancerT 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...
Pyruvate dehydrogenase kinase isoform 2 activity stimulated by speeding up the rate of dissociation of ADPHaiying 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...
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 monomerAli 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...
Pyruvate dehydrogenase kinase isoform 2 activity limited and further inhibited by slowing down the rate of dissociation of ADPHaiying 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...
Facilitated interaction between the pyruvate dehydrogenase kinase isoform 2 and the dihydrolipoyl acetyltransferaseYasuaki Hiromasa
Department of Biochemistry, Kansas State University, Manhattan, Kansas 66506, USA
J Biol Chem 278:33681-93. 2003....
Ligand-induced effects on pyruvate dehydrogenase kinase isoform 2Yasuaki 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...
Structural requirements within the lipoyl domain for the Ca2+-dependent binding and activation of pyruvate dehydrogenase phosphatase isoform 1 or its catalytic subunitAli 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...
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, Nov3rYasuaki 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...
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 componentsYasuaki 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...
Critical role of specific ions for ligand-induced changes regulating pyruvate dehydrogenase kinase isoform 2Yasuaki 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...
Regulatory roles of the N-terminal domain based on crystal structures of human pyruvate dehydrogenase kinase 2 containing physiological and synthetic ligandsThorsten 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...
Autoreactivity to lipoate and a conjugated form of lipoate in primary biliary cirrhosisSylvaine 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 data have implications for patients taking lipoic acid as a dietary supplement...
Structures of the human pyruvate dehydrogenase complex cores: a highly conserved catalytic center with flexible N-terminal domainsXuekui 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 Grants
- REGULATION OF MAMMALIAN PYRUVATE DEHYDROGENASETHOMAS 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. ..
- REGULATION OF MAMMALIAN PYRUVATE DEHYDROGENASETHOMAS ROCHE; Fiscal Year: 1990....
- REGULATION OF MAMMALIAN PYRUVATE DEHYDROGENASETHOMAS 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. ..
