The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

Links

 

Gene Review

DLD  -  dihydrolipoamide dehydrogenase

Homo sapiens

Synonyms: DLDD, DLDH, Dihydrolipoamide dehydrogenase, Dihydrolipoyl dehydrogenase, mitochondrial, E3, ...
 
 
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.
 

Disease relevance of DLD

 

Psychiatry related information on DLD

 

High impact information on DLD

 

Chemical compound and disease context of DLD

 

Biological context of DLD

 

Anatomical context of DLD

  • Fibroblasts cultured from the patient contained only approximately 6% of the E3 activity of cells from a normal subject [20].
  • To study regulation of E3 gene expression, a 12-kilobase clone from a human leukocyte genomic library was isolated, and a 1.8-kilobase fragment containing part of the first intron, the first exon, and 1.5 kilobases of the 5' flanking region of the E3 gene was sequenced [19].
  • Activities of the pyruvate dehydrogenase complex and E3 from patient were 26 and 2% of controls in blood lymphocytes, and 11 and 14% in cultured skin fibroblasts, respectively [21].
  • One of the peptides was found to be dihydrolipoamide dehydrogenase, a membrane enzyme, and one was identified as a sarcomere specific creatine kinase [22].
  • We hypothesize that the IgM on the surface of the naïve B-cell first recognizes an as yet unidentified antigen, and that accumulation of somatic mutations results in an intermolecular epitope shift directed towards an epitope involving the E1/E3 binding domain [23].
 

Associations of DLD with chemical compounds

 

Physical interactions of DLD

 

Enzymatic interactions of DLD

  • Analysis of the pattern of release of E1 and E1' polypeptides from the OGDC during tryptic inactivation suggests that both polypeptide chains of individual E1 homodimers must be cleaved to permit the dissociation of the E1 and E3 components [27].
 

Regulatory relationships of DLD

 

Other interactions of DLD

 

Analytical, diagnostic and therapeutic context of DLD

  • Western and Northern blot analyses indicated that, compared to control cells, the patient's cells had a reduced amount of protein but normal amounts of E3 mRNA [20].
  • The structural organization of the gene for the E3 subunit of the human alpha-ketoacid dehydrogenase complexes, dihydrolipoamide dehydrogenase (DLD), and its upstream elements have been determined by restriction endonuclease mapping and DNA sequence analysis of overlapping genomic clones [34].
  • To investigate the meaning and importance of the Thr conservation in many E3s, the corresponding residue, Thr-44, in human E3 was substituted to Val by site-directed mutagenesis [5].
  • Denaturing HPLC was used to search for sequence variations in the coding and flanking regions of all exons of DLD, but no abundant variants that alter protein sequence were found [6].
  • The serotypes of VEE isolates were identified by antigen assays, and viruses were characterised genetically by sequencing PCR products generated from the E3 and E2 genes [35].

References

  1. Proteinase 3 and dihydrolipoamide dehydrogenase (E3) are major autoantigens in hepatitis C virus (HCV) infection. Wu, Y.Y., Hsu, T.C., Chen, T.Y., Liu, T.C., Liu, G.Y., Lee, Y.J., Tsay, G.J. Clin. Exp. Immunol. (2002) [Pubmed]
  2. Immunoreactive levels of alpha-ketoglutarate dehydrogenase subunits in Friedreich's ataxia and spinocerebellar ataxia type 1. Mastrogiacomo, F., LaMarche, J., Dozić, S., Lindsay, G., Bettendorff, L., Robitaille, Y., Schut, L., Kish, S.J. Neurodegeneration : a journal for neurodegenerative disorders, neuroprotection, and neuroregeneration. (1996) [Pubmed]
  3. Autoepitope mapping and reactivity of autoantibodies to the dihydrolipoamide dehydrogenase-binding protein (E3BP) and the glycine cleavage proteins in primary biliary cirrhosis. Dubel, L., Tanaka, A., Leung, P.S., Van de Water, J., Coppel, R., Roche, T., Johanet, C., Motokawa, Y., Ansari, A., Gershwin, M.E. Hepatology (1999) [Pubmed]
  4. Asparagine-473 residue is important to the efficient function of human dihydrolipoamide dehydrogenase. Kim, H. J. Biochem. Mol. Biol. (2005) [Pubmed]
  5. Activity of human dihydrolipoamide dehydrogenase is reduced by mutation at threonine-44 of FAD-binding region to valine. Kim, H. J. Biochem. Mol. Biol. (2002) [Pubmed]
  6. Association of the dihydrolipoamide dehydrogenase gene with Alzheimer's disease in an Ashkenazi Jewish population. Brown, A.M., Gordon, D., Lee, H., Caudy, M., Hardy, J., Haroutunian, V., Blass, J.P. Am. J. Med. Genet. B Neuropsychiatr. Genet. (2004) [Pubmed]
  7. Leigh syndrome due to compound heterozygosity of dihydrolipoamide dehydrogenase gene mutations. Description of the first E3 splice site mutation. Grafakou, O., Oexle, K., van den Heuvel, L., Smeets, R., Trijbels, F., Goebel, H.H., Bosshard, N., Superti-Furga, A., Steinmann, B., Smeitink, J. Eur. J. Pediatr. (2003) [Pubmed]
  8. Structure of pressinoic acid: the cyclic moiety of vasopressin. Langs, D.A., Smith, G.D., Stezowski, J.J., Hughes, R.E. Science (1986) [Pubmed]
  9. Altered kinetic properties of the branched-chain alpha-keto acid dehydrogenase complex due to mutation of the beta-subunit of the branched-chain alpha-keto acid decarboxylase (E1) component in lymphoblastoid cells derived from patients with maple syrup urine disease. Indo, Y., Kitano, A., Endo, F., Akaboshi, I., Matsuda, I. J. Clin. Invest. (1987) [Pubmed]
  10. Molecular architecture and mechanism of an icosahedral pyruvate dehydrogenase complex: a multifunctional catalytic machine. Milne, J.L., Shi, D., Rosenthal, P.B., Sunshine, J.S., Domingo, G.J., Wu, X., Brooks, B.R., Perham, R.N., Henderson, R., Subramaniam, S. EMBO J. (2002) [Pubmed]
  11. Sequences directing dihydrolipoamide dehydrogenase (E3) binding are located on the 2-oxoglutarate dehydrogenase (E1) component of the mammalian 2-oxoglutarate dehydrogenase multienzyme complex. Rice, J.E., Dunbar, B., Lindsay, J.G. EMBO J. (1992) [Pubmed]
  12. Targeted disruption of the murine dihydrolipoamide dehydrogenase gene (Dld) results in perigastrulation lethality. Johnson, M.T., Yang, H.S., Magnuson, T., Patel, M.S. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  13. Distribution of dihydrolipoamide acetyltransferase (E2) in the liver and portal lymph nodes of patients with primary biliary cirrhosis: an immunohistochemical study. Joplin, R., Lindsay, J.G., Hubscher, S.G., Johnson, G.D., Shaw, J.C., Strain, A.J., Neuberger, J.M. Hepatology (1991) [Pubmed]
  14. Purification, characterization and function of dihydrolipoamide dehydrogenase from the cyanobacterium Anabaena sp. strain P.C.C. 7119. Serrano, A. Biochem. J. (1992) [Pubmed]
  15. The domain structure of the dihydrolipoyl transacetylase component of the pyruvate dehydrogenase complex from Azotobacter vinelandii. Hanemaaijer, R., de Kok, A., Jolles, J., Veeger, C. Eur. J. Biochem. (1987) [Pubmed]
  16. 2-Oxoacid dehydrogenase multienzyme complexes in the halophilic Archaea? Gene sequences and protein structural predictions. Jolley, K.A., Maddocks, D.G., Gyles, S.L., Mullan, Z., Tang, S.L., Dyall-Smith, M.L., Hough, D.W., Danson, M.J. Microbiology (Reading, Engl.) (2000) [Pubmed]
  17. Structural insight into interactions between dihydrolipoamide dehydrogenase (E3) and E3 binding protein of human pyruvate dehydrogenase complex. Brautigam, C.A., Wynn, R.M., Chuang, J.L., Machius, M., Tomchick, D.R., Chuang, D.T. Structure (2006) [Pubmed]
  18. Cloning and cDNA sequence of the dihydrolipoamide dehydrogenase component human alpha-ketoacid dehydrogenase complexes. Pons, G., Raefsky-Estrin, C., Carothers, D.J., Pepin, R.A., Javed, A.A., Jesse, B.W., Ganapathi, M.K., Samols, D., Patel, M.S. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  19. Characterization of the transcriptional regulatory region of the human dihydrolipoamide dehydrogenase gene. Johanning, G.L., Morris, J.I., Madhusudhan, K.T., Samols, D., Patel, M.S. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  20. Identification of two missense mutations in a dihydrolipoamide dehydrogenase-deficient patient. Liu, T.C., Kim, H., Arizmendi, C., Kitano, A., Patel, M.S. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  21. Identification of two mutations in a compound heterozygous child with dihydrolipoamide dehydrogenase deficiency. Hong, Y.S., Kerr, D.S., Craigen, W.J., Tan, J., Pan, Y., Lusk, M., Patel, M.S. Hum. Mol. Genet. (1996) [Pubmed]
  22. Autoantibodies in sera of patients with myocarditis: characterization of the corresponding proteins by isoelectric focusing and N-terminal sequence analysis. Pankuweit, S., Portig, I., Lottspeich, F., Maisch, B. J. Mol. Cell. Cardiol. (1997) [Pubmed]
  23. Immunogenetic analysis reveals that epitope shifting occurs during B-cell affinity maturation in primary biliary cirrhosis. Potter, K.N., Thomson, R.K., Hamblin, A., Richards, S.D., Lindsay, J.G., Stevenson, F.K. J. Mol. Biol. (2001) [Pubmed]
  24. How dihydrolipoamide dehydrogenase-binding protein binds dihydrolipoamide dehydrogenase in the human pyruvate dehydrogenase complex. Ciszak, E.M., Makal, A., Hong, Y.S., Vettaikkorumakankauv, A.K., Korotchkina, L.G., Patel, M.S. J. Biol. Chem. (2006) [Pubmed]
  25. Crystal structure of human dihydrolipoamide dehydrogenase: NAD+/NADH binding and the structural basis of disease-causing mutations. Brautigam, C.A., Chuang, J.L., Tomchick, D.R., Machius, M., Chuang, D.T. J. Mol. Biol. (2005) [Pubmed]
  26. 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. Hiromasa, Y., Fujisawa, T., Aso, Y., Roche, T.E. J. Biol. Chem. (2004) [Pubmed]
  27. Subunit interactions in the mammalian alpha-ketoglutarate dehydrogenase complex. Evidence for direct association of the alpha-ketoglutarate dehydrogenase and dihydrolipoamide dehydrogenase components. McCartney, R.G., Rice, J.E., Sanderson, S.J., Bunik, V., Lindsay, H., Lindsay, J.G. J. Biol. Chem. (1998) [Pubmed]
  28. Glycine decarboxylase and pyruvate dehydrogenase complexes share the same dihydrolipoamide dehydrogenase in pea leaf mitochondria: evidence from mass spectrometry and primary-structure analysis. Bourguignon, J., Merand, V., Rawsthorne, S., Forest, E., Douce, R. Biochem. J. (1996) [Pubmed]
  29. Molecular biology of the human pyruvate dehydrogenase complex: structural aspects of the E2 and E3 components. Thekkumkara, T.J., Pons, G., Mitroo, S., Jentoft, J.E., Patel, M.S. Ann. N. Y. Acad. Sci. (1989) [Pubmed]
  30. Humoral and cellular immune responses to dihydrolipoamide dehydrogenase (E3): lack of specificity for primary biliary cirrhosis. Tanaka, H., Maeda, T., Onishi, S., Yamamoto, Y. Liver (1995) [Pubmed]
  31. Myeloperoxidase-generated phenothiazine cation radicals inactivate Trypanosoma cruzi dihydrolipoamide dehydrogenase. Gutiérrez-Correa, J., Stoppani, A.O. Rev. Argent. Microbiol. (2002) [Pubmed]
  32. A novel mutation in the dihydrolipoamide dehydrogenase E3 subunit gene (DLD) resulting in an atypical form of alpha-ketoglutarate dehydrogenase deficiency. Odièvre, M.H., Chretien, D., Munnich, A., Robinson, B.H., Dumoulin, R., Masmoudi, S., Kadhom, N., Rötig, A., Rustin, P., Bonnefont, J.P. Hum. Mutat. (2005) [Pubmed]
  33. Deficiency of the pyruvate dehydrogenase component in pyruvate dehydrogenase complex-deficient human fibroblasts. Immunological identification. Ho, L., Hu, C.W., Packman, S., Patel, M.S. J. Clin. Invest. (1986) [Pubmed]
  34. The structure of the human dihydrolipoamide dehydrogenase gene (DLD) and its upstream elements. Feigenbaum, A.S., Robinson, B.H. Genomics (1993) [Pubmed]
  35. Re-emergence of epidemic Venezuelan equine encephalomyelitis in South America. VEE Study Group. Weaver, S.C., Salas, R., Rico-Hesse, R., Ludwig, G.V., Oberste, M.S., Boshell, J., Tesh, R.B. Lancet (1996) [Pubmed]
 
WikiGenes - Universities