DAVID CHUANG

Summary

Affiliation: University of Texas Southwestern Medical Center
Country: USA

Publications

  1. ncbi request reprint Lessons from genetic disorders of branched-chain amino acid metabolism
    David T Chuang
    Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390 9038, USA
    J Nutr 136:243S-9S. 2006
  2. ncbi request reprint Cross-talk between thiamin diphosphate binding and phosphorylation loop conformation in human branched-chain alpha-keto acid decarboxylase/dehydrogenase
    Jun Li
    Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9038, USA
    J Biol Chem 279:32968-78. 2004
  3. ncbi request reprint Roles of His291-alpha and His146-beta' in the reductive acylation reaction catalyzed by human branched-chain alpha-ketoacid dehydrogenase: refined phosphorylation loop structure in the active site
    R Max Wynn
    Departments of Biochemistry and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9038, USA
    J Biol Chem 278:43402-10. 2003
  4. ncbi request reprint Structural and biochemical basis for novel mutations in homozygous Israeli maple syrup urine disease patients: a proposed mechanism for the thiamin-responsive phenotype
    Jacinta L Chuang
    Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Biol Chem 279:17792-800. 2004
  5. pmc Distinct structural mechanisms for inhibition of pyruvate dehydrogenase kinase isoforms by AZD7545, dichloroacetate, and radicicol
    Masato Kato
    Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Structure 15:992-1004. 2007
  6. pmc Structural basis for inactivation of the human pyruvate dehydrogenase complex by phosphorylation: role of disordered phosphorylation loops
    Masato Kato
    Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390 9038, USA
    Structure 16:1849-59. 2008
  7. pmc A synchronized substrate-gating mechanism revealed by cubic-core structure of the bovine branched-chain alpha-ketoacid dehydrogenase complex
    Masato Kato
    Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
    EMBO J 25:5983-94. 2006
  8. pmc Pyruvate dehydrogenase kinase-4 structures reveal a metastable open conformation fostering robust core-free basal activity
    R Max Wynn
    Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390 9038, USA
    J Biol Chem 283:25305-15. 2008
  9. ncbi request reprint Encapsulation of an 86-kDa assembly intermediate inside the cavities of GroEL and its single-ring variant SR1 by GroES
    Jiu Li Song
    Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas 75390, USA
    J Biol Chem 278:2515-21. 2003
  10. ncbi request reprint Crystal structure of human dihydrolipoamide dehydrogenase: NAD+/NADH binding and the structural basis of disease-causing mutations
    Chad A Brautigam
    Department of Biochemistry, The University of Texas, Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390 9038, USA
    J Mol Biol 350:543-52. 2005

Research Grants

Collaborators

Detail Information

Publications25

  1. ncbi request reprint Lessons from genetic disorders of branched-chain amino acid metabolism
    David T Chuang
    Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390 9038, USA
    J Nutr 136:243S-9S. 2006
    ..Our results provide a biochemical model for the effectiveness of thiamin therapy to thiamin-responsive MSUD patients...
  2. ncbi request reprint Cross-talk between thiamin diphosphate binding and phosphorylation loop conformation in human branched-chain alpha-keto acid decarboxylase/dehydrogenase
    Jun Li
    Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9038, USA
    J Biol Chem 279:32968-78. 2004
    ..Our results establish that the cross-talk between the bound ThDP and the phosphorylation loop conformation serves as a feed-forward switch for multiple reaction steps in the BCKD metabolic machine...
  3. ncbi request reprint Roles of His291-alpha and His146-beta' in the reductive acylation reaction catalyzed by human branched-chain alpha-ketoacid dehydrogenase: refined phosphorylation loop structure in the active site
    R Max Wynn
    Departments of Biochemistry and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9038, USA
    J Biol Chem 278:43402-10. 2003
    ....
  4. ncbi request reprint Structural and biochemical basis for novel mutations in homozygous Israeli maple syrup urine disease patients: a proposed mechanism for the thiamin-responsive phenotype
    Jacinta L Chuang
    Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Biol Chem 279:17792-800. 2004
    ..The present results offer a structural and biochemical basis for these novel mutations and will facilitate DNA-based diagnosis for MSUD in the Israeli population...
  5. pmc Distinct structural mechanisms for inhibition of pyruvate dehydrogenase kinase isoforms by AZD7545, dichloroacetate, and radicicol
    Masato Kato
    Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Structure 15:992-1004. 2007
    ..Finally, radicicol inhibits kinase activity by binding directly to the ATP-binding pocket of PDK3, similar to Hsp90 and Topo VI from the same ATPase/kinase superfamily...
  6. pmc Structural basis for inactivation of the human pyruvate dehydrogenase complex by phosphorylation: role of disordered phosphorylation loops
    Masato Kato
    Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390 9038, USA
    Structure 16:1849-59. 2008
    ..This results in the disruption of the substrate channeling in the PDC, leading to the inactivation of this catalytic machine...
  7. pmc A synchronized substrate-gating mechanism revealed by cubic-core structure of the bovine branched-chain alpha-ketoacid dehydrogenase complex
    Masato Kato
    Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
    EMBO J 25:5983-94. 2006
    ..We suggest that this gating mechanism synchronizes the binding of the two substrates to the active-site channel, which serves as a feed-forward switch to coordinate the E2b-catalyzed acyltransfer reaction...
  8. pmc Pyruvate dehydrogenase kinase-4 structures reveal a metastable open conformation fostering robust core-free basal activity
    R Max Wynn
    Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390 9038, USA
    J Biol Chem 283:25305-15. 2008
    ..We propose that PDK4 with bound ADP exists in equilibrium between the open and the closed conformations. The favored metastable open conformation is responsible for the robust basal activity of PDK4 in the absence of the PDC core...
  9. ncbi request reprint Encapsulation of an 86-kDa assembly intermediate inside the cavities of GroEL and its single-ring variant SR1 by GroES
    Jiu Li Song
    Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas 75390, USA
    J Biol Chem 278:2515-21. 2003
    ....
  10. ncbi request reprint Crystal structure of human dihydrolipoamide dehydrogenase: NAD+/NADH binding and the structural basis of disease-causing mutations
    Chad A Brautigam
    Department of Biochemistry, The University of Texas, Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390 9038, USA
    J Mol Biol 350:543-52. 2005
    ..The mechanisms by which these mutations impede the function of hE3 are discussed...
  11. pmc Subunit and catalytic component stoichiometries of an in vitro reconstituted human pyruvate dehydrogenase complex
    Chad A Brautigam
    Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    J Biol Chem 284:13086-98. 2009
    ..Prior, A. E., Brown, A. E., Cooper, A., Byron, O., and Lindsay, J. G. (2006) J. Biol. Chem. 281, 19772-19780)...
  12. pmc Structural insight into interactions between dihydrolipoamide dehydrogenase (E3) and E3 binding protein of human pyruvate dehydrogenase complex
    Chad A Brautigam
    Department of Biochemistry, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA
    Structure 14:611-21. 2006
    ..A cluster of disease-causing E3 mutations located near the center of the E3BD/E3 interface prevents the efficient recruitment of these E3 variants by E3BP into the PDC, leading to the dysfunction of the PDC catalytic machine...
  13. ncbi request reprint The two active sites in human branched-chain alpha-keto acid dehydrogenase operate independently without an obligatory alternating-site mechanism
    Jun Li
    Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Biol Chem 282:11904-13. 2007
    ..The above results provide evidence that the two active sites in the E1b heterotetramer operate independently during the ThDP-dependent decarboxylation reaction...
  14. ncbi request reprint A novel branched-chain amino acid metabolon. Protein-protein interactions in a supramolecular complex
    Mohammad Mainul Islam
    Department of Biochemistry, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, USA
    J Biol Chem 282:11893-903. 2007
    ..Our results provide evidence for substrate channeling between hBCATm and BCKD complex and formation of a metabolic unit (termed branched-chain amino acid metabolon) that can be influenced by the redox state in mitochondria...
  15. ncbi request reprint A versatile conformational switch regulates reactivity in human branched-chain alpha-ketoacid dehydrogenase
    Mischa Machius
    Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA
    Structure 14:287-98. 2006
    ..Our results illustrate the versatility of the tyrosine switch in coordinating the catalytic events in E1b by modulating the reactivity of reaction intermediates...
  16. ncbi request reprint Structural determinants for cross-talk between pyruvate dehydrogenase kinase 3 and lipoyl domain 2 of the human pyruvate dehydrogenase complex
    Shih Chia Tso
    Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA
    J Biol Chem 281:27197-204. 2006
    ..Our results indicate that the above residues in L2 and residues in the C-terminal region and the lipoyl-binding pocket of PDK3 are critical determinants for the cross-talk between L2 and PDK3, which up-regulates PDK3 activity...
  17. pmc Pivotal role of the C-terminal DW-motif in mediating inhibition of pyruvate dehydrogenase kinase 2 by dichloroacetate
    Jun Li
    Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9038, USA
    J Biol Chem 284:34458-67. 2009
    ..These results implicate the DW-motif anchoring site as a drug target for the inhibition of aberrant PDK activity in cancer and diabetes...
  18. ncbi request reprint The C-terminal hinge region of lipoic acid-bearing domain of E2b is essential for domain interaction with branched-chain alpha-keto acid dehydrogenase kinase
    Jacinta L Chuang
    Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Biol Chem 277:36905-8. 2002
    ..Our data establish that the C-terminal hinge region of LBD containing the above negatively charged residues is essential for the interaction between the lip-LBD construct and BCK...
  19. pmc Crystal structure of pyruvate dehydrogenase kinase 3 bound to lipoyl domain 2 of human pyruvate dehydrogenase complex
    Masato Kato
    Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
    EMBO J 24:1763-74. 2005
    ..We hypothesize that this allosteric mechanism accounts, in part, for E2p-augmented PDK3 activity...
  20. ncbi request reprint Molecular mechanism for regulation of the human mitochondrial branched-chain alpha-ketoacid dehydrogenase complex by phosphorylation
    R Max Wynn
    Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Structure 12:2185-96. 2004
    ..This mechanism provides a paradigm for regulation of mitochondrial alpha-ketoacid dehydrogenase complexes by phosphorylation...
  21. ncbi request reprint An expanded conformation of single-ring GroEL-GroES complex encapsulates an 86 kDa substrate
    Dong Hua Chen
    National Center for Macromolecular Imaging, Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    Structure 14:1711-22. 2006
    ..Encapsulation of the large assembly intermediate is supported by a series of electron cryomicroscopy studies as well as the protection of both alpha and beta subunits of the substrate from tryptic digestion...
  22. ncbi request reprint Solution structure and dynamics of the lipoic acid-bearing domain of human mitochondrial branched-chain alpha-keto acid dehydrogenase complex
    Chi Fon Chang
    Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan 11529, Republic of China
    J Biol Chem 277:15865-73. 2002
    ..The results showed that residues surrounding the lipoyl lysine region comprising the L1 loop and the Lys(44) beta-turn are highly flexible, whereas beta-sheet S1 appears to display a slow conformational exchange process...
  23. ncbi request reprint Structure of the subunit binding domain and dynamics of the di-domain region from the core of human branched chain alpha-ketoacid dehydrogenase complex
    Chi Fon Chang
    Genomics Research Center and Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan 115, Republic of China
    J Biol Chem 281:28345-53. 2006
    ..We conclude that the presence of the interdomain linker restricts the motional freedom of the hbSBD more significantly than hbLBD, and that the linker region likely exists as a soft rod rather than a flexible string in solution...
  24. ncbi request reprint Seeing GroEL at 6 A resolution by single particle electron cryomicroscopy
    Steven J Ludtke
    National Center for Macromolecular Imaging, Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030 USA
    Structure 12:1129-36. 2004
    ..The 6 A resolution cryo-EM GroEL structure clearly demonstrates the veracity and expanding scope of cryo-EM and the single particle reconstruction technique for macromolecular machines...
  25. doi request reprint De novo backbone trace of GroEL from single particle electron cryomicroscopy
    Steven J Ludtke
    National Center for Macromolecular Imaging, Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
    Structure 16:441-8. 2008
    ..This asymmetric conformation is different from previous asymmetric structures, including GroES-bound GroEL, and may represent a "primed state" in the chaperonin pathway...

Research Grants24

  1. Structure and Function of Mitochondrial Protein Kinase
    DAVID CHUANG; Fiscal Year: 2007
    ..This knowledge will have wide implications for understanding conservation in the reaction mechanism for protein kinases involved in signal transduction as well as how this mechanism is perturbed in human diseases. ..
  2. INBORN ERRORS OF METABOLISM IN CELL CULTURE
    DAVID CHUANG; Fiscal Year: 2007
    ..The knowledge obtained from this investigation will provide a framework for developing more effective therapies for MSUD and neonatal lactic acidemias. ..
  3. INBORN ERRORS OF METABOLISM IN CELL CULTURE
    DAVID CHUANG; Fiscal Year: 2009
    ..The knowledge obtained from this investigation will provide a framework for developing more effective therapies for MSUD and neonatal lactic acidemias. ..
  4. Structure and Function of Mitochondrial Protein Kinases
    DAVID CHUANG; Fiscal Year: 2009
    ....
  5. INBORN ERRORS OF METABOLISM IN CELL CULTURE
    David T Chuang; Fiscal Year: 2010
    ..The knowledge obtained from this investigation will provide a framework for developing more effective therapies for MSUD and neonatal lactic acidemias. ..
  6. Structure and Function of Mitochondrial Protein Kinases
    David T Chuang; Fiscal Year: 2010
    ....
  7. Structure and Function of Mitochondrial Protein Kinases
    David T Chuang; Fiscal Year: 2010
    ....
  8. Structure and Function of Mitochondrial Protein Kinase
    DAVID CHUANG; Fiscal Year: 2006
    ..This knowledge will have wide implications for understanding conservation in the reaction mechanism for protein kinases involved in signal transduction as well as how this mechanism is perturbed in human diseases. ..
  9. INBORN ERRORS OF METABOLISM IN CELL CULTURE
    DAVID CHUANG; Fiscal Year: 2005
    ..Information derived from these studies should increase our understanding of the structure/function and macromolecular assembly of the BCKD complex and help develop more effective therapies for MSUD. ..
  10. INBORN ERRORS OF METABOLISM IN CELL CULTURE
    DAVID CHUANG; Fiscal Year: 2000
    ....
  11. Structure and Function of Mitochondrial Protein Kinase
    DAVID CHUANG; Fiscal Year: 2003
    ..This knowledge will have wide implications for understanding conservation in the reaction mechanism for protein kinases involved in signal transduction as well as how this mechanism is perturbed in human diseases. ..
  12. INBORN ERRORS OF METABOLISM IN CELL CULTURE
    David T Chuang; Fiscal Year: 2010
    ..The knowledge obtained from this investigation will provide a framework for developing more effective therapies for MSUD and neonatal lactic acidemias. ..