Functional and structural impact of the most prevalent missense mutations in classic galactosemia

Molecular Genetics and Genomic Medicine

Volumn 2, Issue 6, 2014, Pages 484-496

  Coelho, Ana I ^a   Trabuco, Matilde ^a   Ramos, Ruben ^a   Silva, Maria João ^a   Almeida, Isabel Tavares de ^a   Leandro, Paula ^a   Rivera, Isabel ^a   Vicente, João B ^a  

^a RESEARCH INSTITUTE FOR MEDICINES IMED ULISBOA   (Portugal)

Author keywords

Chemical pharmacological chaperones; Classic galactosemia; GALT; Misfolding; Missense mutations; Protein aggregation; Proteostasis regulators

Indexed keywords

EID: 84942762217     PISSN: None     EISSN: 23249269     Source Type: Journal    
DOI: 10.1002/mgg3.94     Document Type: Article

References (62)

1. Arnold, K., L. Bordoli, J. Kopp, and T. Schwede. 2006. The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling. Bioinformatics 22:195–201.
2. Bang, Y. L., T. T. Nguyen, T. T. Trinh, Y. J. Kim, J. Song, and Y. H. Song. 2009. Functional analysis of mutations in UDP-galactose-4-epimerase (GALE) associated with galactosemia in Korean patients using mammalian GALE-null cells. FEBS J. 276:1952–1961.
3. Bosch, A. M. 2006. Classical galactosaemia revisited. J. Inherit. Metab. Dis. 29:516–525.
4. Bradford, M. M. 1976. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72:248–254.
5. Brenner, C. 2002. Hint, Fhit, and GalT: function, structure, evolution, and mechanism of three branches of the histidine triad superfamily of nucleotide hydrolases and transferases. Biochemistry 41:9003–9014.
6. Calderon, F. R., A. R. Phansalkar, D. K. Crockett, M. Miller, and R. Mao. 2007. Mutation database for the galactose-1-phosphate uridyltransferase (GALT) gene. Hum. Mutat. 28:939–943.
7. Carney, A. E., R. D. Sanders, K. R. Garza, L. A. McGaha, L. J. Bean, B. W. Coffee, et al. 2009. Origins, distribution and expression of the Duarte-2 (D2) allele of galactose-1-phosphate uridylyltransferase. Hum. Mol. Genet. 18:1624–1632.
8. Chhay, J. S., K. K. Openo, J. S. Eaton, M. Gentile, and J. L. Fridovich-Keil. 2008. A yeast model reveals biochemical severity associated with each of three variant alleles of galactose-1P uridylyltransferase segregating in a single family. J. Inherit. Metab. Dis. 31:97–107.
9. Christacos, N. C., M. J. Marson, L. Wells, K. Riehman, and J. L. Fridovich-Keil. 2000. Subcellular localization of galactose-1-phosphate uridylyltransferase in the yeast Saccharomyces cerevisiae. Mol. Genet. Metab. 70:272–280.
10. Coelho, A. I., R. Ramos, A. Gaspar, C. Costa, A. Oliveira, L. Diogo, et al. 2013. A frequent splicing mutation and novel missense mutations color the updated mutational spectrum of classic galactosemia in Portugal. J. Inherit. Metab. Dis. 37:43–52.
11. Coss, K. P., P. P. Doran, C. Owoeye, M. B. Codd, N. Hamid, P. D. Mayne, et al. 2013. Classical Galactosaemia in Ireland: incidence, complications and outcomes of treatment. J. Inherit. Metab. Dis. 36:21–27.
12. De-Souza, E. A., F. S. Pimentel, C. M. Machado, L. S. Martins, W. S. da-Silva, M. Montero-Lomeli, C. A. Masuda. 2014. The unfolded protein response has a protective role in yeast models of classic galactosemia. Dis. Model. Mech. 7:55–61.
13. Elsas, L. J., II, S. Langley, E. M. Paulk, L. N. Hjelm, and P. P. Dembure. 1995. A molecular approach to galactosemia. Eur. J. Pediatr. 154:S21–S27.
14. Elsas, L. J., K. Lai, C. J. Saunders, and S. D. Langley. 2001. Functional analysis of the human galactose-1-phosphate uridyltransferase promoter in Duarte and LA variant galactosemia. Mol. Genet. Metab. 72:297–305.
15. Evers, T. H., M. A. Appelhof, E. W. Meijer, and M. Merkx. 2008. His-tags as Zn(II) binding motifs in a protein-based fluorescent sensor. Protein Eng. Des. Sel. 21:529–536.
16. Facchiano, A., and A. Marabotti. 2010. Analysis of galactosemia-linked mutations of GALT enzyme using a computational biology approach. Protein Eng. Des. Sel. 23:103–113.
17. Field, T. L., W. S. Reznikoff, and P. A. Frey. 1989. Galactose-1-phosphate uridylyltransferase: identification of histidine-164 and histidine-166 as critical residues by site-directed mutagenesis. Biochemistry 28:2094–2099.
18. Fridovich-Keil, J. L. 2006. Galactosemia: the good, the bad, and the unknown. J. Cell. Physiol. 209:701–705.
19. Fridovich-Keil, J. L., and S. Jinks-Robertson. 1993. A yeast expression system for human galactose-l-phosphate uridylyltransferase. Proc. Natl Acad. Sci. USA 90:398–402.
20. Fridovich-Keil, J. L., and J. H. Walter. 2008. Galactosemia. Pp. 1–92 in A. L. Beaudet, B. Vogelstein, K. W. Kinzler, S. E. Antonarakis, A. Ballabio, and D. Valle, eds. The online metabolic and molecular bases of inherited disease. Mc-Graw Hill, New York, NY.
21. Fridovich-Keil, J. L., S. D. Langley, L. A. Mazur, J. C. Lennon, P. P. Dembure, and L. J. Elsas II. 1995a. Identification and functional analysis of three distinct mutations in the human galactose-1-phosphate uridyltransferase gene associated with galactosemia in a single family. Am. J. Hum. Genet. 56:640–646.
22. Fridovich-Keil, J. L., B. B. Quimby, L. Wells, L. A. Mazur, and J. P. Elsevier. 1995b. Characterization of the N314D allele of human galactose-1-phosphate uridylyltransferase using a yeast expression system. Biochem. Mol. Med. 56:121–130.
23. Geeganage, S., and P. A. Frey. 1998. Transient kinetics of formation and reaction of the uridylyl-enzyme form of galactose-1-P uridylyltransferase and its Q168R-variant: insight into the molecular basis of galactosemia. Biochemistry 37:14500–14507.
24. Geeganage, S., and P. A. Frey. 1999. Significance of metal ions in galactose-1-phosphate uridylyltransferase: an essential structural zinc and a nonessential structural iron. Biochemistry 38:13398–13406.
25. Gregersen, N., P. Bross, S. Vang, and J. H. Christensen. 2006. Protein misfolding and human disease. Annu. Rev. Genomics Hum. Genet. 7:103–124.
26. Hirokawa, H., Y. Okano, M. Asada, A. Fujimoto, I. Suyama, and G. Isshiki. 1999. Molecular basis for phenotypic heterogeneity in galactosaemia: prediction of clinical phenotype from genotype in Japanese patients. Eur. J. Hum. Genet. 7:757–764.
27. Holden, H. M., I. Rayment, and J. B. Thoden. 2003. Structure and function of enzymes of the Leloir pathway for galactose metabolism. J. Biol. Chem. 278:43885–43888.
28. Holton, J. B., J. H. Walter, and L. A. Tyfield. 2001. Galactosemia. Pp. 1553–1587 in C. R. Scriver, A. L. Beaudet, W. S. Sly, and D. Valle, eds. The metabolic and molecular bases of inherited disease. McGraw-Hill, New York, NY.
29. Jumbo-Lucioni, P. P., M. L. Hopson, D. Hang, Y. Liang, D. P. Jones, and J. L. Fridovich-Keil. 2013. Oxidative stress contributes to outcome severity in a Drosophila melanogaster model of classic galactosemia. Dis. Model Mech. 6:84–94.
30. Kiefer, F., K. Arnold, M. Kunzli, L. Bordoli, and T. Schwede. 2009. The SWISS-MODEL Repository and associated resources. Nucleic Acids Res. 37(No. Suppl. 1): D387–D392.
31. Kubota, H., A. Kitamura, and K. Nagata. 2011. Analyzing the aggregation of polyglutamine-expansion proteins and its modulation by molecular chaperones. Methods 53:267–274.
32. Lai, K., and L. J. Elsas. 2001. Structure-function analyses of a common mutation in blacks with transferase-deficiency galactosemia. Mol. Genet. Metab. 74:264–272.
33. Lai, K., S. D. Langley, R. H. Singh, P. P. Dembure, L. N. Hjelm, and L. J. Elsas II. 1996. A prevalent mutation for galactosemia among black Americans. J. Pediatr. 128:89–95.
34. Lai, K., S. D. Langley, P. P. Dembure, L. N. Hjelm, and L. J. Elsas II. 1998. The Duarte allele impairs biostability of galactose-1-phosphate uridyltransferase in human lymphoblasts. Hum. Mutat. 11:28–38.
35. Lai, K., A. C. Willis, and L. J. Elsas II. 1999. The biochemical role of glutamine 188 in human galactose-1-phosphate uridyltransferase. J. Biol. Chem. 274:6559–6566.
36. Langley, S. D., K. Lai, P. P. Dembure, L. N. Hjelm, and L. J. Elsas II. 1997. Molecular basis for Duarte and Los Angeles variant galactosemia. Am. J. Hum. Genet. 60:366–372.
37. Leandro, P., and C. M. Gomes. 2008. Protein misfolding in conformational disorders: rescue of folding defects and chemical chaperoning. Mini-Rev. Med. Chem. 8:901–911.
38. Leslie, N. D. 2003. Insights into the pathogenesis of galactosemia. Annu. Rev. Nutr. 23:59–80.
39. Lindhout, M., M. E. Rubio-Gozalbo, J. A. Bakker, and J. Bierau. 2010. Direct non-radioactive assay of galactose-1-phosphate:uridyltransferase activity using high performance liquid chromatography. Clin. Chim. Acta 411:980–983.
40. Maniatis, T., E. F. Fritsch, and J. Sambrook. 1982. Molecular cloning. A laboratory manual. Cold Spring Harbor, New York, NY.
41. Marabotti, A., and A. Facchiano. 2005. Homology modeling studies on human galactose-1-phosphate uridylyltransferase and on its galactosemia-related mutant Q188R provide an explanation of molecular effects of the mutation on homo-and heterodimers. J. Med. Chem. 48:773–779.
42. McCorvie, T. J., and D. J. Timson. 2011. Structural and molecular biology of type I galactosemia: disease-associated mutations. IUBMB Life 63:949–954.
43. McCorvie, T. J., T. J. Gleason, J. L. Fridovich-Keil, and D. J. Timson. 2013. Misfolding of galactose 1-phosphate uridylyltransferase can result in type I galactosemia. Biochim. Biophys. Acta 1832:1279–1293.
44. Niesen, F. H., H. Berglund, and M. Vedadi. 2007. The use of differential scanning fluorimetry to detect ligand interactions that promote protein stability. Nat. Protoc. 2:2212–2221.
45. Pedersen, C. B., P. Bross, V. S. Winter, T. J. Corydon, L. Bolund, K. Bartlett, et al. 2003. Misfolding, degradation, and aggregation of variant proteins. The molecular pathogenesis of short chain acyl-CoA dehydrogenase (SCAD) deficiency. J. Biol. Chem. 278:47449–47458.
46. Pettersen, E. F., T. D. Goddard, C. C. Huang, G. S. Couch, D. M. Greenblatt, E. C. Meng, et al. 2004. UCSF Chimera–a visualization system for exploratory research and analysis. J. Comput. Chem. 25:1605–1612.
47. Reichardt, J. K., S. Packman, and S. L. C. Woo. 1991. Molecular characterization of two galactosemia mutations: correlation of mutations with highly conserved domains in galactose-1-phosphate uridyl transferase. Am. J. Hum. Genet. 49:860–867.
48. Riehman, K., C. Crews, and J. L. Fridovich-Keil. 2001. Relationship between genotype, activity, and galactose sensitivity in yeast expressing patient alleles of human galactose-1-phosphate uridylyltransferase. J. Biol. Chem. 276:10634–10640.
49. Ruzicka, F. J., J. E. Wedekind, J. Kim, I. Rayment, and P. A. Frey. 1995. Galactose-1-phosphate uridylyltransferase from Escherichia coli, a zinc and iron metalloenzyme. Biochemistry 34:5610–5617.
50. Saunders, H. M., and S. P. Bottomley. 2009. Multi-domain misfolding: understanding the aggregation pathway of polyglutamine proteins. Protein Eng. Des. Sel. 22:447–451.
51. Slepak, T. I., M. Tang, V. Z. Slepak, and K. Lai. 2007. Involvement of endoplasmic reticulum stress in a novel Classic Galactosemia model. Mol. Genet. Metab. 92:78–87.
52. Suchy, F. J., R. J. Sokol, and W. F. Balistreri. 2007. Inborn errors of carbohydrate metabolism. Pp. 595–625 in R. J. Sokol, W. F. Balistreri, and F. S. Suchy, eds. Liver Disease in Children. Cambridge University Press, New York.
53. Suzuki, M., C. West, and E. Beutler. 2001. Large-scale molecular screening for galactosemia alleles in a pan-ethnic population. Hum. Genet. 109:210–215.
54. Thoden, J. B., F. J. Ruzicka, P. A. Frey, I. Rayment, and H. M. Holden. 1997. Structural analysis of the H166G site-directed mutant of galactose-1-phosphate uridylyltransferase complexed with either UDP-glucose or UDP-galactose: detailed description of the nucleotide sugar binding site. Biochemistry 36:1212–1222.
55. ' upstream region of the GALT gene reduces promoter efficiency. Hum. Genet. 109:117–120.
56. Tyfield, L., J. K. Reichardt, J. L. Fridovich-Keil, D. T. Croke, L. J. Elsas II, W. Strobl, et al. 1999. Classical galactosemia and mutations at the galactose-1-phosphate uridyl transferase (GALT) gene. Hum. Mutat. 13:417–430.
57. Waggoner, D. D., N. R. M. Buist, and G. N. Donnel. 1990. Long-term prognosis in galactosaemia: results of a survey of 350 cases. J. Inherit. Metab. Dis. 13:802–818.
58. Wedekind, J. E., P. A. Frey, and I. Rayment. 1995. Three-dimensional structure of galactose-1-phosphate uridylyltransferase from Escherichia coli at 1.8 ÅA resolution. Biochemistry 34:11049–11061.
59. Wedekind, J. E., P. A. Frey, and I. Rayment. 1996. The structure of nucleotidylated histidine-166 of galactose-1-phosphate uridylyltransferase provides insight into phosphoryl group transfer. Biochemistry 35:11560–11569.
60. Wells, L., and J. L. Fridovich-Keil. 1997. Biochemical characterization of the S135L allele of galactose-1-phosphate uridylyltransferase associated with galactosaemia. J. Inherit. Metab. Dis. 20:633–642.
61. Wong, L.-J., and P. A. Frey. 1974. Galactose-1-phosphate uridylyltransferase. Rate studies confirming a uridylyl-enzyme intermediate on the catalytic pathway. Biochemistry 13:3889–3894.
62. Zekanowski, C., B. Radomyska, and J. Bal. 1999. Molecular characterization of Polish patients with classical galactosaemia. J. Inher. Metab. Dis. 22:679–682.