Disease-causing missense mutations affect enzymatic activity, stability and oligomerization of glutaryl-CoA dehydrogenase (GCDH)

Human Molecular Genetics

Volumn 17, Issue 24, 2008, Pages 3854-3863

  Keyser, Britta ^a   Mühlhausen, Chris ^a   Dickmanns, Achim ^b   Christensen, Ernst ^c   Muschol, Nicole ^a   Ullrich, Kurt ^a   Braulke, Thomas ^a  

^a UNIVERSITY MEDICAL CENTER HAMBURG EPPENDORF   (Germany)

^b UNIVERSITY OF GÖTTINGEN   (Germany)

^c Rigshospitalet   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

ADENINE; ARGININE; CYTOSINE; GLUTAMIC ACID; GLUTARYL COENZYME A DEHYDROGENASE; GLYCINE; GUANINE; LYSINE; METHIONINE; THYMINE; TRYPTOPHAN; VALINE;

ANIMAL CELL; ARTICLE; AUTOSOMAL RECESSIVE DISORDER; CELLULAR DISTRIBUTION; CONTROLLED STUDY; ENZYME ACTIVITY; ENZYME STABILITY; GLUTARIC ACIDURIA TYPE 1; HETEROLOGOUS EXPRESSION; MISSENSE MUTATION; MITOCHONDRION; MOLECULAR MODEL; MUTANT; NONHUMAN; OLIGOMERIZATION; PRIORITY JOURNAL; PROTEIN CROSS LINKING; PROTEIN EXPRESSION; PROTEIN PROTEIN INTERACTION; WESTERN BLOTTING; WILD TYPE;

AMINO ACID METABOLISM, INBORN ERRORS; AMINO ACID SUBSTITUTION; ANIMALS; CATALYSIS; CELL LINE; CRICETINAE; ENZYME ACTIVATION; ENZYME STABILITY; GENE EXPRESSION REGULATION; GENES, RECESSIVE; GLUTARATES; GLUTARYL-COA DEHYDROGENASE; HUMANS; MITOCHONDRIAL PROTEINS; MUTATION, MISSENSE; PROTEIN STRUCTURE, QUATERNARY;

MAMMALIA;

EID: 57049138178     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/ddn284     Document Type: Article

References (24)

1. Dwyer, T.M., Rao, K.S., Westover, J.B., Kim, J.-J.P. and Frerman, F.E. (2001) The function of Arg-94 in the oxidation and decarboxylation of glutaryl-CoA by human glutaryl-CoA dehydrogenase. J. Biol. Chem., 276, 133-138.
2. Goodman, S.I. and Frerman, F.E. (2001) Organic acidemias due to defects in lysine oxidation: 2-ketoadipic acidemia and glutaric acidemia. In Scriver, C.R., Beaudet, A.L., Sly, W.S., Valle, D., Childs, B., Kinzler, K.W. and Vogelstein, B. (eds), The Metabolic and Molecular Bases of Inherited Disease, 8th edn. McGraw-Hill Inc., New York, USA, pp. 2195-2204.
3. Kölker, S., Garbade, S.F., Greenberg, C.R., Leonard, J.V., Saudubray, J.-M., Ribes, A.,Kalkanoglu, S., Lund, A.M., Merinero,B., Wajner, M. et al. (2006) Natural history, outcome, and treatment efficacy in children and adults with glutaryl-CoA dehydrogenase deficiency. Pediatr. Res., 59, 840-846.
4. Mühlhausen, C., Hoffmann, G.F., Strauss, K.A., Kölker, S., Okun, J.G., Greenberg, C.R., Naughten, E.R. and Ullrich, K. (2004) Maintenance treatment of glutaryl-CoA-dehydrogenase deficiency. J. Inherit. Metab. Dis., 27, 885-892.
5. Lindner, M., Kölker, S., Schulze, A., Christensen, E., Greenberg, C.R. and Hoffmann, G.F. (2004) Neonatal screening for glutaryl-CoA dehydrogenase deficiency. J. Inherit. Metab. Dis., 27, 851-859.
6. Biery, B.J., Stein, D.E., Morton, D.H. and Goodman, S.I. (1996) Gene structure and mutations of glutaryl-coenzyme A dehydrogenase: Impaired association of enzyme subunits that is due to an A421V substitution causes glutaric acidemia type I in the Amish. Am. J. Hum. Genet., 59, 1006-1011.
7. Goodman, S.I., Kratz, L.E., DiGiulio, K.A., Biery, B.J., Goodman, K.E., Isaya, G. and Frerman, F.E. (1995) Cloning of glutaryl-CoA dehydrogenase cDNA, and expression of wild type and mutant enzymes in Escherichia coli. Hum. Mol. Genet., 4, 1493-1498.
8. Goodman, S.I., Stein, D.E., Schlesinger, S., Christensen, E., Schwartz, M., Greenberg, C.R. and Elpeleg, O.N. (1998) Glutaryl-CoA dehydrogenase mutations in glutaric acidemia (type I): Review and report of thirty novel mutations. Hum. Mutat., 12, 141-144.
9. Schwartz, M., Christensen, E., Superti-Furga, A. and Brandt, N.J. (1998) The human glutaryl-CoA dehydrogenase gene: Report of intronic sequences and of 13 novel mutations causing glutaric aciduria type I. Hum. Genet., 102, 452-458.
10. Busquets, C., Merinero, B., Christensen, E., Gelpi, J.L., Campistol, J., Pineda, M., Fernandez-Alvarez, E., Prats, J.M., Sans, A., Arteaga, R. et al. (2000) Glutaryl-CoA dehydrogenase deficiency in Spain: evidence of two groups of patients, genetically, and biochemically distinct. Pediatr. Res., 48, 315-322.
11. Zschocke, J., Quak, E., Guldberg, P. and Hoffmann, G.F. (2000) Mutation analysis in glutaric aciduria type I. J. Med. Genet., 37, 177-181.
12. Greenberg, C.R., Reimer, D., Singal, R., Triggs-Raine, B., Chudley, A.E., Dilling, L.A., Philipps, S., Haworth, J.C., Seargeant, L.E. and Goodman, S.I. (1995) A G-to-T transversion at the +5 position of intron 1 in the glutaryl CoA dehydrogenase gene is associated with the Island Lake variant of glutaric acidemia type I. Hum. Mol. Genet., 4 493-495.
13. Christensen, E., Ribes, A., Merinero, B. and Zschocke, J. (2004) Correlation of genotype and phenotype in glutaryl-CoA dehydrogenase deficiency. J. Inherit. Metab. Dis., 27, 861-868.
14. Pineda, M., Ribes, A., Busquets, C., Vilaseca, M.A., Aracil, A. and Christensen, E. (1998) Glutaric aciduria type I with high residual glutaryl-CoA dehydrogenase activity. Dev. Med. Child Neurol., 40, 840-842.
15. Mühlhausen, C., Christensen, E., Schwartz, M., Muschol, N., Ullrich, K. and Lukacs, Z. (2003) Severe phenotype despite high residual glutaryl-CoA dehydrogenase activity: A novel mutation in a Turkish patient with glutaric aciduria type 1. J. Inherit. Metab. Dis., 27, 713-714.
16. Westover, J.B., Goodman, S.I. and Frerman, F.E. (2003) Pathogenic mutations in the carboxyl-terminal domain of glutaryl-CoA dehydrogenase: effects on catalytic activity and the stability of the tetramer. Mol. Genet. Metab., 79, 245-256.
17. Rao, K.S., Fu, Z., Albro, M., Narayanan, B., Baddam, S., Lee, H.-J.K., Kim, J.-J.P. and Frerman, F.E. (2007) The effect of a Glu370Asp mutation in glutaryl-CoA dehydrogenase on proton transfer to the dienolate intermediate. Biochemistry, 46, 14468-14477.
18. Fu, Z., Wang, M., Paschke, R., Rao, K.S., Frerman, F.E. and Kim, J.P. (2004) Crystal structures of human glutaryl-CoA dehydrogenase with and without an alternate substrate: Structural bases of dehydrogenation and decarboxylation reactions. Biochemistry, 43, 9674-9684.
19. Koppen, M. and Langer, T. (2007) Protein degradation within mitochondria: Versatile activities of AAA proteases and other peptidases. Crit. Rev. Biochem. Mol. Biol., 42, 221-242.
20. Toogood, H.S., Leys, D. and Scrutton, N.S. (2007) Dynamics driving function - new insights from electron transferring flavoproteins and partner complexes. FEBS J., 274, 5481-5504.
21. Stellmer, F., Keyser, B., Burckhardt, B.C., Koepsell, H., Streichert, T., Glatzel, M., Jabs, S., Thiem, J., Herdering, W., Koeller, D.M. et al. (2007) 3-Hydroxyglutaric acid is transported via the sodium-dependent dicarboxylate transporter NaDC3. J. Mol. Med., 85, 763-770.
22. Muschol, N., Matzner, U., Tiede, S., Gieselmann, V., Ullrich, K. and Braulke, T. (2002) Secretion of phosphomannosyl-deficient arylsulphatase A and cathepsin D from isolated human macrophages. Biochem. J., 368, 845-853.
23. Christensen, E. (1983) Improved assay of glutaryl-CoA dehydrogenase in cultured cells and liver: Application to glutaric aciduria type I. Clin. Chim. Acta, 129, 91-97.
24. Wallace, A.C., Laskowski, R.A. and Thornton, J.M. (1995) LIGPLOT: A program to generate schematic diagrams of protein-ligand interactions. Protein Eng., 8, 127-134.