Recent Publications:

Original Articles:

1.     Brunetti-Pierri, N., Lanpher, B., Erez, A., Ananieva, E.A., Islam, M., C. Marini, J.C., Sun, Q., Yu, C., Hegde. M., Li, J., Wynn, R.M., Chuang, D.T., Hutson, S., and Lee, B.

Phenylbutyrate Therapy for Maple Sryup Urine Disease. Human Molecular Genetics, in press.


  1. Islam, M. M., Nautiyal, M., Wynn, R.M., Mobley, J. A., Chuang, D. T., and Hutson, S.M.
    Branched-chain amino acid metabolon: interaction of glutamate dehydrogenase with the mitochondrial branched-chain aminotransferase (BCATm).
    J. Biol. Chem. 285, 265-276, 2010


  1. Li, J., Kato, M., and Chuang, D. T.
    Pivotal role of the C-terminal DW-motif in mediating inhibition of pyruvate dehydrogenase kinase 2 by dichloroacetate.
    J. Biol. Chem. 284, 34458-34467, 2009


  1. Georgiou, T., Chuang, J. L., Wynn, R. M., Stylianidou, G., Korson, M., Chuang, D. T., and Drousiotou, A.
    Maple syrup urine disease in Cypriot families: identification of three novel mutations and biochemical characterization of the p.Thr211Met mutation in the E1alpha subunit.
    Genet. Test Mol. Biomarkers. 13, 657-664, 2009


  1. Brautigam, C. A., Wynn, R. M., Chuang, J. L., and Chuang, D. T.
    Subunit and catalytic-component stoichiometries of an in vitro reconstituted human pyruvate dehydrogenase complex. J. Biol. Chem. In press.


  1. Kato, M., Wynn, R. M., Chuang, J. L., Tso, S.-C., Machius, M., Li, J. and Chuang, D. T.
    Structural Basis for Inactivation of the Human Pyruvate Dehydrogenase Complex by Phosphorylation: Role of Disordered Phosphorylation Loops. Structure, 16, 1849-59, 2008


  1. Wynn, R. M., Kato, M., Chuang, J. L., Tso, S.-C., Li, J. and Chuang, D. T.
    Pyruvate dehydrogenase kinase-4 structures reveal a metastable open conformation fostering robust core-free basal activity. J Biol Chem. 283, 25305-25315, 2008


  1. Ludtke, S. J., Baker, M.L., Chen, D.-H., Song, J.-L., Chuang, D.T. and Chiu, W.
    De Novo Backbone Trace of GroEL from Single Particle Electron Cryomicroscopy. Structure 16, 441-448, 2008
  2. Kato, M., Li, J., Chuang, J. L. and Chuang, D. T.
    Distinct Structural Mechanisms for Inhibition of Pyruvate Dehydrogenase Kinase Isoforms by AZD7545, Dichloroacetate and Radicicol. Structure 15, 992-1004, 2007
  3. Li,  J., Machius, M., Chuang, J. L., Wynn, R. M. and Chuang, D. T.
    The two active sites in human branched-chain α-ketoacid dehydrogenase operate independently without an obligatory alternating-site mechanism. J Biol Chem. 282, 11904-13, 2007


  1. Islam, M. M., Wallin, R., Wynn, R. M. Conway, M., Fujii, H., Mobley, J. A., Chuang, D. T. and Hutson, S. M.
    A novel branched-chain amino acid metabolon: Protein-protein interactions in a supramolecular complex. J Biol Chem. 282, 11893-903, 2007

  2. Kato, M., Wynn, R. M., Chuang, J. L., Brautigam, C. A., Custorio, M. and Chuang, D. T.
    A synchronized substrate-gating mechanism revealed by cubic-core structure of the bovine branched-chain α-ketoacid dehydrogenase complex.
    EMBO J. 25, 5983-5994, 2006
  3. Chen, D.-H., Song, J.-L., Chuang, D. T., Chiu, W. and Ludtke, S. J.
    An Expanded Conformation of Single-Ring GroEL-GroES Complex Encapsulates an 86 kDa Substrate. Structure14, 1711-1722, 2006
  4. Chang, C. F., Chou, H. T., Lin, Y. J., Lee, S. J., Chuang, J. L., Chuang, D. T. and Huang, T. H.
    Structure of the subunit binding domain and dynamics of the di-domain region from the core of human branched-chain α-ketoacid dehydrogenase complex. J. Biol. Chem. 281, 28345-353, 2006


  1. Tso, C.-S., Kato, M., Chuang, J. L. and Chuang, D. T.
    Structural determinants for cross-talk between pyruvate dehydrogenase kinase 3 and lipoyl domain 2 of the human pyruvate dehydrogenase complex. J. Biol. Chem. 281, 27197–204, 2006


  1. Brautigam, C. A., Wynn, R. M., Chuang, J. L., Machius, M., Tomchick, D. R. and Chuang, D. T.
    Structural insight into interactions between dihydrolipoamide dehydrogenase (E3) and E3 binding protein of human pyruvate dehydrogenase complex. Structure 14, 611-21.


  1. Machius, M., Wynn, R. M., Chuang, J. L., Li, J., Kluger, R., Yu, D., Tomchick, D. R., Brautigam, C. A. and Chuang, D. T.
    A versatile conformational switch regulates reactivity in human branched-chain α-ketoacid dehydrogenase. Structure 14, 287-298.


  1. Chuang, D. T., Chuang, J. L. and Wynn, R. M.
    Lessons from genetic disorders of branched-chain amino acid metabolism. J Nutr 136, 243S-9S.

  2. Brautigam, C. A., Chuang, J. L., Tomchick, D. R., Machius, M. and Chuang, D. T.
    Crystal structure of human dihydrolipoamide dehydrogenase: NAD+/NADH binding and the structural basis of disease-causing mutations. J. Mol. Biol. 350, 543-552, 2005
  3. Kato, M., Chuang, J. L., Tso, C.-S., Wynn, R. M. and Chuang, D. T.
    Crystal structure of pyruvate dehydrogenase kinase 3 bound to lipoyl domain 2 of human pyruvate dehydrogenase complex. EMBO J. 24, 1763-1774, 2005
  4. Wynn, R. M., Kato, M., Machius, M., Chuang, J. L., Li, J., Tomchick, D. R., and Chunag, D. T.
    Molecular mechanism for regulation of the human mitochondrial branched-chain α-ketoacid dehydrogenase complex by phosphorylation. Structure 12, 2185-96, 2004


  1. Ludtke, S., Chen, D., Song, J.-L., Chuang, D.T., and Chiu, W.
    Seeing GroEL at 6 Å resolution by single particle electron cryomicroscopy. Structure 12, 1129-36, 2004

23.   Li, J., Wynn, R. M., Machius, M., Chuang, J. L., Karthikeyan, S., Tomchick, D. R., and Chuang, D. T.
Crosstalk between cofactor binding and the phosphorylation loop conformation in the BCKD metabolic machine. J. Biol. Chem. 279, 32968-78, 2004

24.   Chuang, J.L., Wynn, R.M., Moss, C.C., Song, J.L., Li, J., Awad, N., Mandel, H., and Chuang, D.T.
Structural and biochemical basis for novel mutations in homozygous Israeli maple syrup urine disease patients: A proposed mechanism for thiamin-responsive phenotype. J. Biol. Chem. 279, 17792-17800, 2004

25.   Wynn, R. M., Machius, M., Chuang, J. L., Li, J., Tomchick, D. R., and Chuang, D. T.
Roles of His291-α and His146-β' in the reductive acylation reaction catalyzed by human branched-chain α-ketoacid dehydrogenase. Refined phosphorylation loop structure in the active site. J. Biol. Chem. 278, 43402-43410, 2003

26.   Song, J.-L., Li. J., Huang, Y.-S., and Chuang, D. T.
Encapsulation of an 86-kDa assembly intermediate inside the cavities of GroEL and Its single-ring variant SR1 by GroES.
J Biol Chem. 278, 2515-2521, 2003.

27.   Chuang, J. L., Wynn, R. M., and Chuang, D. T.
The C-terminal hinge region of lipoic acid-bearing domain of E2b is essential for domain interaction with branched-chain α-keto acid dehydrogenase kinase. J. Biol Chem. 277, 36905-36908, 2002.

  1. Chang, C.-F., Chou, H.-T., Chuang, J.L., Chuang, D.T., and Huang, T.-H.
    Solution structure of the lipoic acid-bearing domain of human mitochondrial branched-chain α-ketoacid dehydrogenase complex. J. Biol. Chem. 277, 15865-15873, 2002.

29.   Song, J.-L., and Chuang, D. T.
Natural osmolyte trimethylamine N-oxide corrects assembly defects of mutant branched-chain α-ketoacid dehydrogenase in maple syrup urine disease. J. Biol. Chem. 276, 40241-6, 2001.

30.   Ludtke, S., Jakana, J., Tsuruta, H., Song, J.-L., Chuang, D. T., and Chiu, W.
A 11.5 A single particle reconstruction of GroEL using EMAN. J. Mol. Biol. 314, 253-262, 2001.

31.   Machius, M., Chuang, J. L., Wynn, R. M., Tomchick, D. R., and Chuang, D. T.
Structure of rat BCKD kinase: nucleotide-induced domain communication in a mitochondrial protein kinase. Proc. Natl. Acad. Sci. U.S.A. 98, 11218-23, 2001.

32.   Wynn, R. M., Chuang, J. L., Sansaricq, C., Mandel H., and Chuang, D. T.
Biochemical basis of Type IB (E1beta) mutations in maple syrup urine disease. A prevalent allele in patients from the Druze kindred in Israel. J. Biol. Chem. 276, 36550-56, 2001.

33.   Wynn, R. M., Ho, R., Chuang, J. L., and Chuang, D. T.
Roles of active-site and novel K+-ion binding-site residues in human mitochondrial branched-chain α-ketoacid decarboxylase/dehydrogenase. J. Biol. Chem. 276, 4168-4174, 2001.

34.   Wynn, R.M., Chuang, J. L., Cote, C. D. and Chuang, D. T.
Tetrameric assembly and conservation in the ATP-binding domain of rat branched-chain α-ketoacid dehydrogenase kinase. J. Biol. Chem. 275, 30512-30519, 2000.

35.   Song, J.-L., Wynn. R.M., and Chuang, D.T.
Interactions of GroEL/GroES with a heterodimeric intermediate during α2β2 assembly of mitochondrial branched-chain α-ketoacid dehydrogenase. Cis capping of the native-like 86-kDa intermediate by GroES. J. Biol. Chem. 275, 22305-22312, 2000.

36.   Æevarsson, A.,Chuang, J.L., Wynn, R.M., Turley, S., Chuang, D.T., and Hol, W.G.H.
Crystal structure of human branched-chain α-ketoacid dehydrogenase and molecular basis of multienzyme complex deficiency in maple syrup urine disease. Structure. 8, 277-291, 2000.

37.   Wynn, R.M., Song, J.-L, and Chuang, D.T.
GroEL/GroES promote dissociation/reassociation cycles of a heterodimeric intermediate during α2β2 oligomeric assembly. Iterative annealing at the quaternary structure level. J. Biol.Chem. 275, 2786-2794, 2000.

38.   Lebo, R. V., Shapiro, L. R., Fenerco, E. Y., Hoover, J. M., Chuang, J. L., Chuang, D. T., and Kronn, D. F.
Rare etiology of autosomal recessive disease in a child with non-carrier parents. Am. J. Hum. Genet. 67, 750-754, 2000.

39.   Huang, Y.S. and Chuang, D.T.
Regulation of BCKD kinase gene expression in hepatoma cells and rat liver. Methods Enzymol. 324, 498-511, 2000.

40.   Chuang, J.L., Davie, J.R., Wynn, R.M. and Chuang, D.T.
Production of recombinant holo-E2 and reconstitution of BCKD complex with recombinant E1 and E3. Methods Enzymol. 324, 192-200, 2000.

41.   Chuang, J.L. and Chuang, D.T.
Diagnosis and mutational analysis of maple syrup urine disease. Methods Enzymol. 324, 413-423, 2000.

42.   Wynn, R.M.. Davie, J.R., Song, J.-L., Chuang, J.L., and Chuang, D.T.
Expression of E1 component of human branched-chain α-keto acid dehydrogenase complex in Escherichia coli by cotransformation with chaperonins GroEL and GroES. Methods Enzymol. 324, 179-191, 2000.

43.   Huang, Y.S., and Chuang, D.T.
Down-regulation of the rat mitochondrial branched-chain 2-oxo-acid dehydrogenase kinase gene expression by glucocorticoids. Biochem. J. 339, 503-510, 1999.

44.   Chuang, J.L., Wynn, R.M., Song, J.-L., and Chuang, D.T.
GroEL/GroES-dependent reconstitution of α2β2 tetramers of human mitochondrial branched-chain α-ketoacid decarboxylase in vitro. Obligatory interaction of chaperonins with an α2β2 dimeric intermediate. J. Biol. Chem. 274, 10395-10404, 1999.

45.   Huang, Y.S., and Chuang, D.T.
Mechanisms for GroEL/GroES-mediated folding of a large 86-kDa fusion polypeptide in vitro. J. Biol. Chem. 274, 10405-10412, 1999.


Invited Review Chapters:

1.     Chuang, D. T., Wynn, R. M., and Chuang, J.L. Three-dimensional structures for components and domains of the mammalian branched-chain α-ketoacid dehydrogenase complex. In "Thiamin: Catalytic Mechanisms and Roles in Normal and Disease States" (Jordan, F., and Patel, M. S. eds.) Marcel Dekker, Inc., New York, pp. 449-469, 2004.

2.     Chuang D. T. Oxidation of branched-chain α-keto acids. In "Encyclopedia of Biological Chemistry" (Lennarz, J., and Lane, M. D. eds.) Academic Press/Elsevier Science, San Diego/New York, (in press), 2004.

3.     Chuang, D.T, Cox, R.P., and Chuang, J.L. Maple syrup urine disease: Clinical and biochemical perspectives. In "The Molecular and Genetic Basis of Neurological Disease" (Eds. Rosenberg, R.N., Prusiner, S.B., DiMauro, S., Barchi, R.L., and Kunkel, L.M.), 3rd Edition, Butterworths Publ., London, pp. 635-642, 2003.

4.     Chuang, D. T.,Chuang, J. L., Wynn, R. M., and Song, J.-L. The branched-chain α-keto acid dehydrogenase complex, human. In"Ecyclopedia of Molecular Medicine" (Creighton, T. E., ed.) Vol. 5, John Wiley & Sons, New York, New York, pp. 393-396 , 2001.

5.     Chuang, D.T., and Shih, V.E. Maple syrup urine disease (Branched-chain ketoaciduria). In: "The Metabolic and Molecular Basis of Inherited Disease" (Eds. Scriver, C.R., Beaudet, A.L., Sly, W.S. and Valle, D., Vogelstein, B., Childs, B.) 8th Edition, McGraw-Hill, New York, pp.1971-2006, 2001.

6.     Chuang, D.T. Maple syrup urine disease: It has come a long way. J. Pediatr. 132, S17-S23, 1998.